In vivo pharmacology of endocannabinoids and their metabolic inhibitors: Therapeutic implications in Parkinson's disease and abuse liability

Prostaglandins and Other Lipid Mediators

Volumn 91, Issue 3-4, 2010, Pages 90-103

  Giuffrida, Andrea ^a   McMahon, Lance R ^a  

^a Mays Cancer Center at UT Health San Antonio   (United States)

Author keywords

2 Arachidonyl glycerol; Anandamide; Cannabinoid; Drug abuse; Dyskinesia; FAAH; Levodopa; MAGL; Marijuana

Indexed keywords

1 (2,4 DICHLOROPHENYL) 5 (4 IODOPHENYL) 4 METHYL N (1 PIPERIDYL) 1H PYRAZOLE 3 CARBOXAMIDE; 2 ARACHIDONOYL GLYCEROL; 2,3 DIHYDRO 5 METHYL 3 (MORPHOLINOMETHYL) 6 (1 NAPHTHOYL)PYRROLO[1,2,3 DE][1,4]BENZOXAZINE; 4 (1,1 DIMETHYLHEPTYL) 1',2',3',4',5',6' HEXAHYDRO 2,3' DIHYDROXY 6' (3 HYDROXYPROPYL)BIPHENYL; 4 AMINOBUTYRIC ACID RECEPTOR; ACYLGLYCEROL LIPASE; ANANDAMIDE; ARACHIDONYLCYCLOPROPYLAMIDE; CANNABINOID 1 RECEPTOR AGONIST; CANNABINOID 2 RECEPTOR; CANNABINOID RECEPTOR AGONIST; CANNABINOID RECEPTOR ANTAGONIST; CANNABIS; CAPSAZEPINE; CYCLIC AMP DEPENDENT PROTEIN KINASE; CYCLOHEXYLCARBAMIC ACID 3' CARBAMOYLBIPHENYL 3 YL ESTER; DRONABINOL; ENDOCANNABINOID; FATTY ACID AMIDASE INHIBITOR; FOCAL ADHESION KINASE; G PROTEIN COUPLED RECEPTOR; METHANANDAMIDE; MITOGEN ACTIVATED PROTEIN KINASE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PHOSPHOLIPASE C BETA; RHOA GUANINE NUCLEOTIDE BINDING PROTEIN; RIMONABANT; TRANSIENT RECEPTOR POTENTIAL CHANNEL 1; UNCLASSIFIED DRUG; UNINDEXED DRUG; VOLTAGE GATED CALCIUM CHANNEL;

ANTINOCICEPTION; ANXIETY; BASAL GANGLION; BINDING AFFINITY; BRAIN CORTEX; C57BL 6 MOUSE; CATALEPSY; CEREBELLUM; CLINICAL ASSESSMENT; DEACYLATION; DEPRESSION; DOPAMINERGIC SYSTEM; DOSE RESPONSE; DRUG ABUSE; DRUG ACTIVATION; DRUG ANTAGONISM; DRUG BINDING; DRUG BRAIN LEVEL; DRUG DEGRADATION; DRUG DISCRIMINATION; DRUG EFFECT; DRUG HALF LIFE; DRUG INDUSTRY; DRUG MECHANISM; DRUG METABOLISM; DRUG POTENCY; DRUG SELF ADMINISTRATION; DRUG SYNTHESIS; DRUG TARGETING; ENZYME INHIBITION; ENZYME LOCALIZATION; FOOD INTAKE; GENE EXPRESSION; HIPPOCAMPUS; HOMEOSTASIS; HYPOTHERMIA; IMMUNE RESPONSE; IMMUNE SYSTEM; IN VIVO STUDY; INFLAMMATION; INSTRUMENTAL CONDITIONING; INTERNEURON; KNOCKOUT MOUSE; LIPID METABOLISM; LOCOMOTION; MEDICAL LIABILITY; MICROGLIA; MOOD; MOTOR PERFORMANCE; NERVE CELL PLASTICITY; NEUROPATHY; NEUROPROTECTION; NEUROTRANSMISSION; NONHUMAN; PAIN; PARKINSON DISEASE; PROTEIN EXPRESSION; RECEPTOR BINDING; RECEPTOR UPREGULATION; REGULATORY MECHANISM; REVIEW; REWARD; SENSORY NERVE; SIGNAL TRANSDUCTION; SMOKING; TRANSCRIPTION INITIATION; VOMITING;

ANIMALS; ENDOCANNABINOIDS; HUMANS; LIGANDS; PARKINSON DISEASE; RECEPTORS, CANNABINOID; SUBSTANCE-RELATED DISORDERS;

EID: 77949489748     PISSN: 10988823     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.prostaglandins.2009.05.004     Document Type: Review

References (267)

1. Piomelli D. The endocannabinoid system: a drug discovery perspective. Curr Opin Investig Drugs 6 7 (2005) 672-679
2. Mackie K., and Stella N. Cannabinoid receptors and endocannabinoids: evidence for new players. AAPS J 8 2 (2006) E298-E306
3. Pertwee R.G., and Ross R.A. Cannabinoid receptors and their ligands. Prostaglandins Leukot Essent Fatty Acids 66 2-3 (2002) 101-121
4. Matsuda L.A., Lolait S.J., Brownstein M., Young A., and Bonner T.I. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346 (1990) 561-564
5. Herkenham M., Lynn A.B., Little M.D., et al. Cannabinoid receptor localization in brain. Proc Natl Acad Sci 87 (1990) 1932-1936
6. Herkenham M. In: Pertwee R.G. (Ed). Cannabinoid receptors (1995), Academic Press, New York pp. 1455-66
7. Glass M., Dragunow M., and Faull R.L.M. Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neuroscience 77 2 (1997) 299-318
8. Munro S., Thomas K.L., and Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 365 (1993) 61-65
9. Lynn A.B., and Herkenham M. Localization of cannabinoid receptors and nonsaturable high-density cannabinoid binding sites in peripheral tissues of the rat: implications for receptor-mediated immune modulation by cannabinoids. J Pharmacol Exp Ther 268 (1994) 1612-1623
10. Klein T.W., Newton C., and Friedman H. Cannabinoid receptors and immunity. Immunol Today 19 8 (1998) 373-381
11. Ashton J.C., Friberg D., Darlington C.L., and Smith P.F. Expression of the cannabinoid CB2 receptor in the rat cerebellum: an immunohistochemical study. Neurosci Lett 396 2 (2006) 113-116
12. Van Sickle M.D., Duncan M., Kingsley P.J., et al. Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science 310 5746 (2005) 329-332
13. Walter L., and Stella N. Cannabinoids and neuroinflammation. Br J Pharmacol 141 5 (2004) 775-785
14. Ramirez B.G., Blazquez C., Gomez del Pulgar T., Guzman M., and de Ceballos M.L. Prevention of Alzheimer's disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. J Neurosci 25 8 (2005) 1904-1913
15. Childers S.R., and Deadwyler S.A. Role of cyclic AMP in the actions of cannabinoid receptors. Biochem Pharmacol 52 6 (1996) 819-827
16. Mukhopadhyay S., McIntosh H.H., Houston D.B., and Howlett A.C. The CB (1) cannabinoid receptor juxtamembrane C-terminal peptide confers activation to specific G proteins in brain. Mol Pharmacol 57 1 (2000) 162-170
17. Mukhopadhyay S., and Howlett A.C. Chemically distinct ligands promote differential CB1 cannabinoid receptor-Gi protein interactions. Mol Pharmacol 67 6 (2005) 2016-2024
18. Glass M., and Felder C.C. Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors augments cAMP accumulation in striatal neurons: evidence for a Gs linkage to the CB1 receptor. J Neurosci 17 14 (1997) 5327-5333
19. Hampson R.E., Mu J., and Deadwyler S.A. Cannabinoid and kappa opioid receptors reduce potassium K current via activation of G (s) proteins in cultured hippocampal neurons. J Neurophysiol 84 5 (2000) 2356-2364
20. Kearn C.S., Blake-Palmer K., Daniel E., Mackie K., and Glass M. Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors enhances heterodimer formation: a mechanism for receptor cross-talk?. Mol Pharmacol 67 (2005) 1697-1704
21. Hojo M., Sudo Y., Ando Y., et al. mu-Opioid receptor forms a functional heterodimer with cannabinoid CB1 receptor: electrophysiological and FRET assay analysis. J Pharmacol Sci 108 3 (2008) 308-319
22. Shoemaker J.L., Ruckle M.B., Mayeux P.R., and Prather P.L. Agonist-directed trafficking of response by endocannabinoids acting at CB2 receptors. J Pharmacol Exp Ther 315 2 (2005) 828-838
23. Mackie K., and Hille B. Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. Proc Natl Acad Sci USA 89 9 (1992) 3825-3829
24. Caulfield M.P., and Brown D.A. Cannabinoid receptor agonists inhibit Ca current in NG108-15 neuroblastoma cells via a pertussis toxin-sensitive mechanism. Br J Pharmacol 106 2 (1992) 231-232
25. 2+ channels in neuronal expression system. Mol Pharmacol 49 4 (1996) 707-714
26. Twitchell W., Brown S., and Mackie K. Cannabinoids inhibit N- and P/Q-type calcium channels in cultured rat hippocampal neurons. J Neurophysiol 78 (1997) 43-50
27. + M-current in hippocampal CA1 neurons. J Neurosci 20 1 (2000) 51-58
28. Mu J., Zhuang S.Y., Kirby M.T., Hampson R.E., and Deadwyler S.A. Cannabinoid receptors differentially modulate potassium A and D currents in hippocampal neurons in culture. J Pharmacol Exp Ther 291 2 (1999) 893-902
29. Hoffman A.F., and Lupica C.R. Mechanisms of cannabinoid inhibition of GABA (A) synaptic transmission in the hippocampus. J Neurosci 20 7 (2000) 2470-2479
30. Wilson R.I., Kunos G., and Nicoll R.A. Presynaptic specificity of endocannabinoid signaling in the hippocampus. Neuron 31 3 (2001) 453-462
31. Kreitzer A.C., and Regehr W.G. Cerebellar depolarization-induced suppression of inhibition is mediated by endogenous cannabinoids. J Neurosci 21 RC174 (2001) 1-5
32. Gerdeman G., and Lovinger D.M. CB1 cannabinoid receptor inhibit synaptic release of glutamate in rat dorsolateral striatum. J Neurophysiol 85 (2001) 468-471
33. Herkenham M., Groen B.G.S., Lynn A.B., De Costa B.R., and Richfield E.K. Neuronal localization of cannabinoid receptors in the basal ganglia of the rat. Brain Res 547 (1991) 267-274
34. Marsicano G., and Lutz B. Expression of the cannabinoid receptor CB1 in distinct neuronal subpopulations in the adult mouse forebrain. Eur J Neurosci 11 12 (1999) 4213-4225
35. Tsou K., Brown S., Sañudo-Peña M.C., Mackie K., and Walker J.M. Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neuroscience 83 (1998) 393-411
36. Katona I., Sperlagh B., Sík A., et al. Presynaptically located CB1 cannabinoid receptors regulate GABA release from axon terminals of specific hippocampal interneurons. J Neurosci 19 11 (1999) 4544-4558
37. Huang C.C., Lo S.W., and Hsu K.S. Presynaptic mechanisms underlying cannabinoid inhibition of excitatory synaptic transmission in rat striatal neurons. J Physiol 532 Pt 3 (2001) 731-748
38. Derkinderen P., Valjent E., Toutant M., et al. Regulation of extracellular signal-regulated kinase by cannabinoids in hippocampus. J Neurosci 23 6 (2003) 2371-2382
39. Ledent C., Valverde O., Cossu G., et al. Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice. Science 283 (1999) 401-404
40. Steiner H., Bonner T.I., Zimmer A.M., Kitai S.T., and Zimmer A. Altered gene expression in striatal projection neurons in CB1 cannabinoid receptor knockout mice. Proc Natl Acad Sci USA 96 10 (1999) 5786-5790
41. Buckley N.E., McCoy K.L., Mezey E., et al. Immunomodulation by cannabinoids is absent in mice deficient for the cannabinoid CB (2) receptor. Eur J Pharmacol 396 2-3 (2000) 141-149
42. Ziring D., Wei B., Velazquez P., Schrage M., Buckley N.E., and Braun J. Formation of B and T cell subsets require the cannabinoid receptor CB2. Immunogenetics 58 9 (2006) 714-725
43. Marsicano G., Wotjak C.T., Azad S.C., et al. The endogenous cannabinoid system controls extinction of aversive memories. Nature 418 6897 (2002) 530-534
44. Begg M., Pacher P., Batkai S., et al. Evidence for novel cannabinoid receptors. Pharmacol Ther 106 2 (2005) 133-145
45. Hájos N., Ledent C., and Freund T.F. Novel cannabinoid-sensitive receptor mediates inhibition of glutamatergic synaptic transmission in the hippocampus. Neuroscience 106 (2001) 1-4
46. Hájos N., and Freund T.F. Distinct cannabinoid sensitive receptors regulate hippocampal excitation and inhibition. Chem Phys Lipids 121 (2002) 73-82
47. Kawamura Y., Fukaya M., Maejima T., et al. The CB1 cannabinoid receptor is the major cannabinoid receptor at excitatory presynaptic sites in the hippocampus and cerebellum. J Neurosci 26 11 (2006) 2991-3001
48. Járai W., Wagner J.A., Varga K., et al. Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors. Proc Natl Acad Sci USA 96 (1999) 14136-14141
49. Sawzdargo M., Nguyen T., Lee D.K., et al. Identification and cloning of three novel human G protein-coupled receptor genes GPR52, PsiGPR53 and GPR55: GPR55 is extensively expressed in human brain. Brain Res Mol Brain Res 64 2 (1999) 193-198
50. Johns D.G., Behm D.J., Walker D.J., et al. The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects. Br J Pharmacol 152 5 (2007) 825-831
51. Ryberg E., Larsson N., Sjogren S., et al. The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol 152 7 (2007) 1092-1101
52. Lauckner J.E., Jensen J.B., Chen H.Y., Lu H.C., Hille B., and Mackie K. GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc Natl Acad Sci USA 105 7 (2008) 2699-2704
53. Brown A.J. Novel cannabinoid receptors. Br J Pharmacol 152 5 (2007) 567-575
54. McPartland J.M., Matias I., Di Marzo V., and Glass M. Evolutionary origins of the endocannabinoid system. Gene 370 (2006) 64-74
55. Staton P.C., Hatcher J.P., Walker D.J., et al. The putative cannabinoid receptor GPR55 plays a role in mechanical hyperalgesia associated with inflammatory and neuropathic pain. Pain 139 1 (2008) 225-236
56. Patapoutian A., Tate S., and Woolf C.J. Transient receptor potential channels: targeting pain at the source. Nat Rev Drug Discov 8 1 (2009) 55-68
57. Caterina M.J., Schumacher M.A., Tominaga M., Rosen T.A., Levine J.D., and Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389 (1997) 816-824
58. Akopian A.N., Ruparel N.B., Jeske N.A., Patwardhan A., and Hargreaves K.M. Role of ionotropic cannabinoid receptors in peripheral antinociception and antihyperalgesia. Trends Pharmacol Sci (2008)
59. Starowicz K., Maione S., Cristino L., et al. Tonic endovanilloid facilitation of glutamate release in brainstem descending antinociceptive pathways. J Neurosci 27 50 (2007) 13739-13749
60. Cristino L., de Petrocellis L., Pryce G., Baker D., Guglielmotti V., and Di Marzo V. Immunohistochemical localization of cannabinoid type 1 and vanilloid transient receptor potential vanilloid type 1 receptors in the mouse brain. Neuroscience 139 4 (2006) 1405-1415
61. Mezey E., Tóth Z.E., Cortright D.N., et al. Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1-like immunoreactivity, in the central nervous system of the rat and human. Proc Natl Acad Sci USA 97 (2000) 3655-3660
62. Moran M.M., Xu H., and Clapham D.E. TRP ion channels in the nervous system. Curr Opin Neurobiol 14 3 (2004) 362-369
63. Marinelli S., Di Marzo V., Berretta N., et al. Presynaptic facilitation of glutamatergic synapses to dopaminergic neurons of the rat substantia nigra by endogenous stimulation of vanilloid receptors. J Neurosci 23 8 (2003) 3136-3144
64. Marsch R., Foeller E., Rammes G., et al. Reduced anxiety, conditioned fear, and hippocampal long-term potentiation in transient receptor potential vanilloid type 1 receptor-deficient mice. J Neurosci 27 4 (2007) 832-839
65. Panlilio L.V., Mazzola C., Medalie J., et al. Anandamide-induced behavioral disruption through a vanilloid-dependent mechanism in rats. Psychopharmacology (Berl) (2008)
66. Morgese M.G., Cassano T., Cuomo V., and Giuffrida A. Anti-dyskinetic effects of cannabinoids in a rat model of Parkinson's disease: role of CB (1) and TRPV1 receptors. Exp Neurol 208 1 (2007) 110-119
67. Zygmunt P.M., Petersson J., Andersson D.A., et al. Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 400 (1999) 452-457
68. Huang S.M., Bisogno T., Trevisani M., et al. An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors. Proc Natl Acad Sci USA 99 12 (2002) 8400-8405
69. De Petrocellis L., Starowicz K., Moriello A.S., Vivese M., Orlando P., and Di Marzo V. Regulation of transient receptor potential channels of melastatin type 8 (TRPM8): effect of cAMP, cannabinoid CB (1) receptors and endovanilloids. Exp Cell Res 313 9 (2007) 1911-1920
70. Watanabe H., Vriens J., Prenen J., Droogmans G., Voets T., and Nilius B. Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels. Nature 424 6947 (2003) 434-438
71. Jordt S.E., Bautista D.M., Chuang H.H., et al. Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature 427 6971 (2004) 260-265
72. Szolcsanyi I. Are cannabinoids endogenous ligands for the VR1 capsaicin receptor. Trends Pharmacol Sci 21 (2000) 41-42
73. Zygmunt P.M., Julius I., Di Marzo I., and Hogestatt E.D. Anandamide-the other side of the coin. Trends Pharmacol Sci 21 2 (2000) 43-44
74. De Petrocellis L., Bisogno T., Maccarrone M., Davis J.B., Finazzi-Agro A., and Di Marzo V. The activity of anandamide at vanilloid VR1 receptors requires facilitated transport across the cell membrane and is limited by intracellular metabolism. J Biol Chem 276 16 (2001) 12856-12863
75. Starowicz K., Nigam S., and Di Marzo V. Biochemistry and pharmacology of endovanilloids. Pharmacol Ther 114 1 (2007) 13-33
76. Patwardhan A.M., Jeske N.A., Price T.J., Gamper N., Akopian A.N., and Hargreaves K.M. The cannabinoid WIN 55, 212-2 inhibits transient receptor potential vanilloid 1 (TRPV1) and evokes peripheral antihyperalgesia via calcineurin. Proc Natl Acad Sci USA 103 30 (2006) 11393-11398
77. Jeske N.A., Patwardhan A.M., Gamper N., Price T.J., Akopian A.N., and Hargreaves K.M. Cannabinoid WIN 55,212-2 regulates TRPV1 phosphorylation in sensory neurons. J Biol Chem (2006)
78. Akopian A.N., Ruparel N.B., Patwardhan A., and Hargreaves K.M. Cannabinoids desensitize capsaicin and mustard oil responses in sensory neurons via TRPA1 activation. J Neurosci 28 5 (2008) 1064-1075
79. Moreno S., Farioli-Vecchioli S., and Ceru M.P. Immunolocalization of peroxisome proliferator-activated receptors and retinoid X receptors in the adult rat CNS. Neuroscience 123 1 (2004) 131-145
80. Cimini A., Benedetti E., Cristiano L., et al. Expression of peroxisome proliferator-activated receptors (PPARs) and retinoic acid receptors (RXRs) in rat cortical neurons. Neuroscience 130 2 (2005) 325-337
81. Ferre P. The biology of peroxisome proliferator-activated receptors: relationship with lipid metabolism and insulin sensitivity. Diabetes 53 Suppl. 1 (2004) S43-S50
82. Glass C.K., and Ogawa S. Combinatorial roles of nuclear receptors in inflammation and immunity. Nat Rev Immunol 6 1 (2006) 44-55
83. Stienstra R., Mandard S., Patsouris D., Maass C., Kersten S., and Muller M. Peroxisome proliferator-activated receptor alpha protects against obesity-induced hepatic inflammation. Endocrinology 148 6 (2007) 2753-2763
84. Martinasso G., Oraldi M., Trombetta A., et al. Involvement of PPARs in cell proliferation and apoptosis in human colon cancer specimens and in normal and cancer cell lines. PPAR Res 2007 (2007) 93416
85. Fu J., Gaetani S., Oveisi F., et al. Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha. Nature 425 6953 (2003) 90-93
86. Breidert T., Callebert J., Heneka M.T., Landreth G., Launay J.M., and Hirsch E.C. Protective action of the peroxisome proliferator-activated receptor-gamma agonist pioglitazone in a mouse model of Parkinson's disease. J Neurochem 82 3 (2002) 615-624
87. Dehmer T., Heneka M.T., Sastre M., Dichgans J., and Schulz J.B. Protection by pioglitazone in the MPTP model of Parkinson's disease correlates with I kappa B alpha induction and block of NF kappa B and iNOS activation. J Neurochem 88 2 (2004) 494-501
88. Heneka M.T., and Landreth G.E. PPARs in the brain. Biochim Biophys Acta 1771 8 (2007) 1031-1045
89. Kliewer S.A., Sundseth S.S., Jones S.A., et al. Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc Natl Acad Sci USA 94 9 (1997) 4318-4323
90. Sun Y., and Bennett A. Cannabinoids: a new group of agonists of PPARs. PPAR Res 2007 (2007) 23513
91. Sun Y., Alexander S.P., Garle M.J., et al. Cannabinoid activation of PPARalpha; a novel neuroprotective mechanism. Br J Pharmacol (2007)
92. Bouaboula M., Hilairet S., Marchand J., Fajas L., Le Fur G., and Casellas P. Anandamide induced PPARgamma transcriptional activation and 3T3-L1 preadipocyte differentiation. Eur J Pharmacol 517 3 (2005) 174-181
93. Melis M., Pillolla G., Luchicchi A., et al. Endogenous fatty acid ethanolamides suppress nicotine-induced activation of mesolimbic dopamine neurons through nuclear receptors. J Neurosci 28 51 (2008) 13985-13994
94. Di Marzo V., Fontana A., Cadas H., et al. Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature 372 (1994) 686-691
95. Schmid H.H. Pathways and mechanisms of N-acylethanolamine biosynthesis: can anandamide be generated selectively?. Chem Phys Lipids 108 1-2 (2000) 71-87
96. Devane W.A., Hanus L., Breuer A., et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258 5090 (1992) 1946-1949
97. Mechoulam R., Ben-Shabat S., Hanus L., et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 50 (1995) 83-90
98. Sugiura T., Kondo S., Sukagawa A., et al. 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem Biophys Res Commun 215 (1995) 89-97
99. Fride E., and Mechoulam R. Pharmacological activity of the cannabinoid receptor agonist, anandamide, a brain constituent. Eur J Pharmacol 231 2 (1993) 313-314
100. Okamoto Y., Morishita J., Tsuboi K., Tonai T., and Ueda N. Molecular characterization of a phospholipase D generating anandamide and its congeners. J Biol Chem 279 7 (2004) 5298-5305
101. Nyilas R., Dudok B., Urban G.M., et al. Enzymatic machinery for endocannabinoid biosynthesis associated with calcium stores in glutamatergic axon terminals. J Neurosci 28 5 (2008) 1058-1063
102. Leung D., Saghatelian A., Simon G.M., and Cravatt B.F. Inactivation of N-acyl phosphatidylethanolamine phospholipase D reveals multiple mechanisms for the biosynthesis of endocannabinoids. Biochemistry 45 15 (2006) 4720-4726
103. Simon G.M., and Cravatt B.F. Endocannabinoid biosynthesis proceeding through glycerophospho-N-acyl ethanolamine and a role for alpha/beta-hydrolase 4 in this pathway. J Biol Chem 281 36 (2006) 26465-26472
104. Liu J., Wang L., Harvey-White J., et al. Multiple pathways involved in the biosynthesis of anandamide. Neuropharmacology 54 1 (2008) 1-7
105. Deutsch D.G., and Chin S.A. Enzymatic synthesis and degradation of anandamide, a cannabinoid receptor agonist. Biochem Pharmacol 46 (1993) 791-796
106. Beltramo M., di Tomaso E., and Piomelli D. Inhibition of anandamide hydrolysis in rat brain tissue by (E)-6-(bromomethylene) tetrahydro-3- (1-naphthalenyl)-2H-pyran-2-one. FEBS Lett 403 (1997) 263-267
107. Fegley D., Kathuria S., Mercier R., et al. Anandamide transport is independent of fatty-acid amide hydrolase activity and is blocked by the hydrolysis-resistant inhibitor AM1172. Proc Natl Acad Sci USA 101 23 (2004) 8756-8761
108. Hillard C.J., Wilkison D.M., Edgemont W.S., and Campbell W.B. Characterization of the kinetics and distribution of N-arachidonylethanolamine (anandamide) hydrolysis by rat brain. Biochim Biophys Acta 1257 (1995) 249-256
109. Cravatt B.F., Giang D.K., Mayfield S.P., Boger D.L., Lerner R.A., and Gilula N.B. Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature 384 (1996) 83-87
110. Glaser S.T., Abumrad N.A., Fatade F., Kaczocha M., Studholme K.M., and Deutsch D.G. Evidence against the presence of an anandamide transporter. Proc Natl Acad Sci USA 100 7 (2003) 4269-4274
111. Hillard C.J., and Jarrahian A. Cellular accumulation of anandamide: consensus and controversy. Br J Pharmacol 140 5 (2003) 802-808
112. Day T.A., Rakhshan F., Deutsch D.G., and Barker E.L. Role of fatty acid amide hydrolase in the transport of the endogenous cannabinoid anandamide. Mol Pharmacol 59 6 (2001) 1369-1375
113. Cravatt B.F., Demarest K., Patricelli M.P., et al. Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase. Proc Natl Acad Sci USA 98 (2001) 9371-9376
114. McFarland M.J., Porter A.C., Rakhshan F.R., Rawat D.S., Gibbs R.A., and Barker E.L. A role for caveolae/lipid rafts in the uptake and recycling of the endogenous cannabinoid anandamide. J Biol Chem 279 40 (2004) 41991-41997
115. Wei B.Q., Mikkelsen T.S., McKinney M.K., Lander E.S., and Cravatt B.F. A second fatty acid amide hydrolase with variable distribution among placental mammals. J Biol Chem 281 48 (2006) 36569-36578
116. Kathuria S., Gaetani S., Fegley D., et al. Modulation of anxiety through blockade of anandamide hydrolysis. Nat Med 1 (2003) 76-81
117. Justinova Z., Mangieri R.A., Bortolato M., et al. Fatty acid amide hydrolase inhibition heightens anandamide signaling without producing reinforcing effects in primates. Biol Psychiatry 64 11 (2008) 930-937
118. Maccarrone M., Rossi S., Bari M., et al. Anandamide inhibits metabolism and physiological actions of 2-arachidonoylglycerol in the striatum. Nat Neurosci 11 2 (2008) 152-159
119. Gobbi G., Bambico F.R., Mangieri R., et al. Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis. Proc Natl Acad Sci USA 102 51 (2005) 18620-18625
120. Maione S., Bisogno T., de Novellis V., et al. Elevation of endocannabinoid levels in the ventrolateral periaqueductal grey through inhibition of fatty acid amide hydrolase affects descending nociceptive pathways via both cannabinoid receptor type 1 and transient receptor potential vanilloid type-1 receptors. J Pharmacol Exp Ther 316 3 (2006) 969-982
121. Yu M., Ives D., and Ramesha C.S. Synthesis of prostaglandin E2 ethanolamide from anandamide by cyclooxtgenase-2. J Biol Chem 272 (1997) 21181-21186
122. Fowler C.J. The contribution of cyclooxygenase-2 to endocannabinoid metabolism and action. Br J Pharmacol 152 5 (2007) 594-601
123. Weber A., Ni J., Ling K.H., et al. Formation of prostamides from anandamide in FAAH knockout mice analyzed by HPLC with tandem mass spectrometry. J Lipid Res 45 4 (2004) 757-763
124. Vila M., Jackson-Lewis V., Guegan C., et al. The role of glial cells in Parkinson's disease. Curr Opin Neurol 14 4 (2001) 483-489
125. Collaco-Moraes Y., Aspey B., Harrison M., and de Belleroche J. Cyclo-oxygenase-2 messenger RNA induction in focal cerebral ischemia. J Cereb Blood Flow Metab 16 6 (1996) 1366-1372
126. Ueda N., Yamamoto K., Yamamoto S., et al. Lipoxygenase-catalyzed oxygenation of arachidonylethanolamide, a cannabinoid receptor agonist. Biochim Biophys Acta 1254 (1995) 127-134
127. Kozak K.R., Gupta R.A., Moody J.S., et al. 15-Lipoxygenase metabolism of 2-arachidonylglycerol. Generation of a peroxisome proliferator-activated receptor alpha agonist. J Biol Chem 277 26 (2002) 23278-23286
128. Snider N.T., Sikora M.J., Sridar C., Feuerstein T.J., Rae J.M., and Hollenberg P.F. The endocannabinoid anandamide is a substrate for the human polymorphic cytochrome P450 2D6. J Pharmacol Exp Ther 327 2 (2008) 538-545
129. Snider N.T., Nast J.A., Tesmer L.A., and Hollenberg P.F. A cytochrome P450-derived epoxygenated metabolite of anandamide is a potent cannabinoid receptor 2-selective agonist. Mol Pharmacol 75 4 (2009) 965-972
130. Kozak K.R., and Marnett L.J. Oxidative metabolism of endocannabinoids. Prostaglandins Leukot Essent Fatty Acids 66 (2002) 211-220
131. Ross R.A. Anandamide and vanilloid TRPV1 receptors. Br J Pharmacol 140 5 (2003) 790-801
132. O'Sullivan S.E. Cannabinoids go nuclear: evidence for activation of peroxisome proliferator-activated receptors. Br J Pharmacol 152 5 (2007) 576-582
133. LoVerme J., Russo R., La Rana G., et al. Rapid broad-spectrum analgesia through activation of peroxisome proliferator-activated receptor-alpha. J Pharmacol Exp Ther 319 3 (2006) 1051-1061
134. Freund T.F., Katona I., and Piomelli D. Role of endogenous cannabinoids in synaptic signaling. Physiol Rev 83 3 (2003) 1017-1066
135. Wilson R.I., and Nicoll R.A. Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. Nature 410 (2001) 588-592
136. Diana M.A., Levenes C., Mackie K., and Marty A. Short-term retrograde inhibition of GABAergic synaptic currents in rat Purkinje cells is mediated by endogenous cannabinoids. J Neurosci 22 1 (2002) 200-208
137. Marinelli S., Pacioni S., Bisogno T., et al. The endocannabinoid 2-arachidonoylglycerol is responsible for the slow self-inhibition in neocortical interneurons. J Neurosci 28 50 (2008) 13532-13541
138. Stella N., Schweitzer P., and Piomelli D. A second endogenous cannabinoid that modulates long-term potentiation. Nature 388 (1997) 773-778
139. Hashimotodani Y., Ohno-Shosaku T., Tsubokawa H., et al. Phospholipase Cbeta serves as a coincidence detector through its Ca2+ dependency for triggering retrograde endocannabinoid signal. Neuron 45 2 (2005) 257-268
140. Bisogno T., Howell F., Williams G., et al. Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain. J Cell Biol 163 3 (2003) 463-468
141. Yoshida T., Fukaya M., Uchigashima M., et al. Localization of diacylglycerol lipase-alpha around postsynaptic spine suggests close proximity between production site of an endocannabinoid, 2-arachidonoyl-glycerol, and presynaptic cannabinoid CB1 receptor. J Neurosci 26 18 (2006) 4740-4751
142. Katona I., Urban G.M., Wallace M., et al. Molecular composition of the endocannabinoid system at glutamatergic synapses. J Neurosci 26 21 (2006) 5628-5637
143. Suarez J., Bermudez-Silva F.J., Mackie K., et al. Immunohistochemical description of the endogenous cannabinoid system in the rat cerebellum and functionally related nuclei. J Comp Neurol 509 4 (2008) 400-421
144. Hashimotodani Y., Ohno-Shosaku T., and Kano M. Ca (2+)-assisted receptor-driven endocannabinoid release: mechanisms that associate presynaptic and postsynaptic activities. Curr Opin Neurobiol 17 3 (2007) 360-365
145. Maejima T., Oka S., Hashimotodani Y., et al. Synaptically driven endocannabinoid release requires Ca2+-assisted metabotropic glutamate receptor subtype 1 to phospholipase Cbeta4 signaling cascade in the cerebellum. J Neurosci 25 29 (2005) 6826-6835
146. Wang J., and Ueda N. Biology of endocannabinoid synthesis system. Prostaglandins Other Lipid Mediat (2008)
147. Beltramo M., and Piomelli D. Carrier-mediated transport and enzymatic hydrolysis of the endogenous cannabinoid 2-arachidonylglycerol. NeuroReport 11 6 (2000) 1231-1235
148. Bisogno T., MacCarrone M., De Petrocellis L., et al. The uptake by cells of 2-arachidonoylglycerol, an endogenous agonist of cannabinoid receptors. Eur J Biochem 268 7 (2001) 1982-1989
149. Fowler C.J., and Ghafouri N. Does the hydrolysis of 2-arachidonoylglycerol regulate its cellular uptake?. Pharmacol Res 58 1 (2008) 72-76
150. Muccioli G.G., Xu C., Odah E., et al. Identification of a novel endocannabinoid-hydrolyzing enzyme expressed by microglial cells. J Neurosci 27 11 (2007) 2883-2889
151. Dinh T.P., Carpenter D., Leslie F.M., et al. Brain monoglyceride lipase participating in endocannabinoid inactivation. Proc Natl Acad Sci USA 99 (2002) 10819-10824
152. Dinh T.P., Kathuria S., and Piomelli D. RNA interference suggests a primary role for monoacylglycerol lipase in the degradation of the endocannabinoid 2-arachidonoylglycerol. Mol Pharmacol 66 5 (2004) 1260-1264
153. Hohmann A.G., Suplita R.L., Bolton N.M., et al. An endocannabinoid mechanism for stress-induced analgesia. Nature 435 7045 (2005) 1108-1112
154. Makara J.K., Mor M., Fegley D., et al. Selective inhibition of 2-AG hydrolysis enhances endocannabinoid signaling in hippocampus. Nat Neurosci 8 9 (2005) 1139-1141
155. Burston J.J., Sim-Selley L.J., Harloe J.P., et al. N-arachidonyl maleimide potentiates the pharmacological and biochemical effects of the endocannabinoid 2-arachidonylglycerol through inhibition of monoacylglycerol lipase. J Pharmacol Exp Ther 327 2 (2008) 546-553
156. Long J.Z., Li W., Booker L., et al. Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects. Nat Chem Biol 5 1 (2009) 37-44
157. Gulyas A.I., Cravatt B.F., Bracey M.H., et al. Segregation of two endocannabinoid-hydrolyzing enzymes into pre- and postsynaptic compartments in the rat hippocampus, cerebellum and amygdala. Eur J Neurosci 20 2 (2004) 441-458
158. Uchigashima M., Narushima M., Fukaya M., Katona I., Kano M., and Watanabe M. Subcellular arrangement of molecules for 2-arachidonoyl-glycerol-mediated retrograde signaling and its physiological contribution to synaptic modulation in the striatum. J Neurosci 27 14 (2007) 3663-3676
159. Kozak K.R., Crews B.C., Morrow J.D., et al. Metabolism of the endocannabinoids, 2-arachidonylglycerol and anandamide, into prostaglandin, thromboxane, and prostacyclin glycerol esters and ethanolamides. J Biol Chem 277 47 (2002) 44877-44885
160. Sang N., Zhang J., and Chen C. PGE2 glycerol ester, a COX-2 oxidative metabolite of 2-arachidonoyl glycerol, modulates inhibitory synaptic transmission in mouse hippocampal neurons. J Physiol 572 Pt 3 (2006) 735-745
161. Kim J., and Alger B.E. Inhibition of cyclooxygenase-2 potentiates retrograde endocannabinoid effects in hippocampus. Nat Neurosci 7 7 (2004) 697-698
162. Kirkham T.C., and Tucci S.A. Endocannabinoids in appetite control and the treatment of obesity. CNS Neurol Disord Drug Targets 5 3 (2006) 272-292
163. Witkin J.M., Tzavara E.T., Davis R.J., Li X., and Nomikos G.G. A therapeutic role for cannabinoid CB1 receptor antagonists in major depressive disorders. Trends Pharmacol Sci 26 12 (2005) 609-617
164. Mangieri R.A., and Piomelli D. Enhancement of endocannabinoid signaling and the pharmacotherapy of depression. Pharmacol Res 56 5 (2007) 360-366
165. Solinas M., Goldberg S.R., and Piomelli D. The endocannabinoid system in brain reward processes. Br J Pharmacol 154 2 (2008) 369-383
166. Moreira F.A., and Lutz B. The endocannabinoid system: emotion, learning and addiction. Addict Biol 13 2 (2008) 196-212
167. Fernandez-Ruiz J. The endocannabinoid system as a target for the treatment of motor dysfunction. Br J Pharmacol (2009)
168. Stella N. Endocannabinoid signaling in microglial cells. Neuropharmacology 56 Suppl. 1 (2009) 244-253
169. Kreitzer F.R., and Stella N. The therapeutic potential of novel cannabinoid receptors. Pharmacol Ther (2009)
170. Hohmann A.G., and Suplita II R.L. Endocannabinoid mechanisms of pain modulation. AAPS J 8 4 (2006) E693-E708
171. Anand P., Whiteside G., Fowler C.J., and Hohmann A.G. Targeting CB (2) receptors and the endocannabinoid system for the treatment of pain. Brain Res Rev (2008)
172. Martin B.R., Compton D.R., Thomas B.F., et al. Behavioral, biochemical, and molecular modeling evaluations of cannabinoid analogs. Pharmacol Biochem Behav 40 (1991) 471-478
173. Balster R.L., and Prescott W.R. Delta 9-tetrahydrocannabinol discrimination in rats as a model for cannabis intoxication. Neurosci Biobehav Rev 16 1 (1992) 55-62
174. 9-tetrahydrocannabinol-induced responses and apparent agonist activity. J Pharmacol Exp Ther 277 2 (1996) 586-594
175. Willoughby K.A., Moore S.F., Martin B.R., and Ellis E.F. The biodisposition and metabolism of anandamide in mice. J Pharmacol Exp Ther 282 1 (1997) 243-247
176. Smith P.B., Compton D.R., Welch S.P., Razdan R.K., Mechoulam R., and Martin B.R. The pharmacological activity of anandamide, a putative endogenous cannabinoid, in mice. J Pharmacol Exp Ther 270 1 (1994) 219-227
177. Lichtman A.H., Hawkins E.G., Griffin G., and Cravatt B.F. Pharmacological activity of fatty acid amides is regulated, but not mediated, by fatty acid amide hydrolase in vivo. J Pharmacol Exp Ther 302 (2002) 73-79
178. Wiley J.L., Razdan R.K., and Martin B.R. Evaluation of the role of the arachidonic acid cascade in anandamide's in vivo effects in mice. Life Sci 80 1 (2006) 24-35
179. Adams I.B., Compton D.R., and Martin B.R. Assessment of anandamide interaction with the cannabinoid brain receptor: SR141716A antagonism studies in mice and autoradiographic analysis of receptor binding in rat brain. J Pharmacol Exp Ther 284 (1998) 1209-1217
180. Welch S.P., Huffman J.W., and Lowe J. Differential blockade of the antinociceptive effects of centrally administered cannabinoids by SR141716A. J Pharmacol Exp Ther 286 3 (1998) 1301-1308
181. Di Marzo V., Breivogel C.S., Tao Q., et al. Levels, metabolism, and pharmacological activity of anandamide in CB1 cannabinoid receptor knockout mice: evidence for non-CB1, non-CB2 receptor-mediated actions of anandamide in mouse brain. J Neurochem 75 (2000) 2434-2444
182. McMahon L.R., and Koek W. Differences in the relative potency of SR 141716A and AM 251 as antagonists of various in vivo effects of cannabinoid agonists in C57BL/6J mice. Eur J Pharmacol 569 1-2 (2007) 70-76
183. Jarbe T.U., Andrzejewski M.E., and DiPatrizio N.V. Interactions between the CB1 receptor agonist Delta 9-THC and the CB1 receptor antagonist SR-141716 in rats: open-field revisited. Pharmacol Biochem Behav 73 4 (2002) 911-919
184. Wiley J., Balster R., and Martin B. Discriminative stimulus effects of anandamide in rats. Eur J Pharmacol 276 1-2 (1995) 49-54
185. Jarbe T.U., Lamb R.J., Lin S., and Makriyannis A. (R)-methanandamide and Delta 9-THC as discriminative stimuli in rats: tests with the cannabinoid antagonist SR-141716 and the endogenous ligand anandamide. Psychopharmacology (Berl) 156 4 (2001) 369-380
186. Solinas M., Tanda G., Justinova Z., et al. The endogenous cannabinoid anandamide produces delta-9-tetrahydrocannabinol-like discriminative and neurochemical effects that are enhanced by inhibition of fatty acid amide hydrolase but not by inhibition of anandamide transport. J Pharmacol Exp Ther 321 1 (2007) 370-380
187. McMahon L.R., Ginsburg B.C., and Lamb R.J. Cannabinoid agonists differentially substitute for the discriminative stimulus effects of Delta (9)-tetrahydrocannabinol in C57BL/6J mice. Psychopharmacology (Berl) 198 4 (2008) 487-495
188. Wiley J.L., Golden K.M., Ryan W.J., Balster R.L., Razdan R.K., and Martin B.R. Evaluation of cannabimimetic discriminative stimulus effects of anandamide and methylated fluoroanandamide in rhesus monkeys. Pharmacol Biochem Behav 58 4 (1997) 1139-1143
189. Abadji V., Lin S., Taha G., et al. (R)-methanandamide: a chiral novel anandamide possessing higher potency and metabolic stability. J Med Chem 37 (1994) 1889-1893
190. Jarbe T.U., Liu Q., and Makriyannis A. Antagonism of discriminative stimulus effects of delta (9)-THC and (R)-methanandamide in rats. Psychopharmacology (Berl) 184 1 (2006) 36-45
191. Jarbe T.U., DiPatrizio N.V., Li C., and Makriyannis A. Effects of AM1346, a high-affinity CB1 receptor selective anandamide analog, on open-field behavior in rats. Behav Pharmacol 18 7 (2007) 673-680
192. Jarbe T.U., Sheppard R., Lamb R.J., Makriyannis A., Lin S., and Goutopoulos A. Effects of delta-9-tetrahydrocannabinol and (R)-methanandamide on open-field behavior in rats. Behav Pharmacol 9 2 (1998) 169-174
193. Hillard C.J., Manna S., Greenberg M.J., et al. Synthesis and characterization of potent and selective agonists of the neuronal cannabinoid receptor (CB1). J Pharmacol Exp Ther 289 3 (1999) 1427-1433
194. McMahon L.R. Apparent affinity estimates of rimonabant in combination with anandamide and chemical analogs of anandamide in rhesus monkeys discriminating Delta (9)-tetrahydrocannabinol. Psychopharmacology (Berl) (2008)
195. Baskfield C.Y., Martin B.R., and Wiley J.L. Differential effects of delta9-tetrahydrocannabinol and methanandamide in CB1 knockout and wild-type mice. J Pharmacol Exp Ther 309 1 (2004) 86-91
196. Petitet F., Jeantaud B., Bertrand P., and Imperato A. Cannabinoid penetration into mouse brain as determined by ex vivo binding. Eur J Pharmacol 374 3 (1999) 417-421
197. Compton D.R., and Martin B.R. The effect of the enzyme inhibitor phenylmethylsulfonyl fluoride on the pharmacological effect of anandamide in the mouse model of cannabimimetic activity. J Pharmacol Exp Ther 283 (1997) 1138-1143
198. Moss D.E., Rodriguez L.A., and McMaster S.B. Comparative behavioral effects of CNS cholinesterase inhibitors. Pharmacol Biochem Behav 22 3 (1985) 479-482
199. Fegley D., Gaetani S., Duranti A., et al. Characterization of the fatty acid amide hydrolase inhibitor cyclohexyl carbamic acid 3′-carbamoyl-biphenyl-3-yl ester (URB597): effects on anandamide and oleoylethanolamide deactivation. J Pharmacol Exp Ther 313 1 (2005) 352-358
200. Lichtman A.H., Leung D., Shelton C.C., et al. Reversible inhibitors of fatty acid amide hydrolase that promote analgesia: evidence for an unprecedented combination of potency and selectivity. J Pharmacol Exp Ther 311 2 (2004) 441-448
201. Boger D.L., Miyauchi H., Du W., et al. Discovery of a potent, selective, and efficacious class of reversible alpha-ketoheterocycle inhibitors of fatty acid amide hydrolase effective as analgesics. J Med Chem 48 6 (2005) 1849-1856
202. Naidu P.S., Varvel S.A., Ahn K., Cravatt B.F., Martin B.R., and Lichtman A.H. Evaluation of fatty acid amide hydrolase inhibition in murine models of emotionality. Psychopharmacology (Berl) 192 1 (2007) 61-70
203. Scherma M., Medalie J., Fratta W., et al. The endogenous cannabinoid anandamide has effects on motivation and anxiety that are revealed by fatty acid amide hydrolase (FAAH) inhibition. Neuropharmacology 54 1 (2008) 129-140
204. Mallet P.E., and Beninger R.J. Delta9-tetrahydrocannabinol, but not the endogenous cannabinoid receptor ligand anandamide, produces conditioned place avoidance. Life Sci 62 26 (1998) 2431-2439
205. Lichtman A.H., Shelton C.C., Advani T., and Cravatt B.F. Mice lacking fatty acid amide hydrolase exhibit a cannabinoid receptor-mediated phenotypic hypoalgesia. Pain 109 3 (2004) 319-327
206. Wise L.E., Cannavacciulo R., Cravatt B.F., Martin B.F., and Lichtman A.H. Evaluation of fatty acid amides in the carrageenan-induced paw edema model. Neuropharmacology (2007)
207. Laine K., Jarvinen K., Mechoulam R., Breuer A., and Jarvinen T. Comparison of the enzymatic stability and intraocular pressure effects of 2-arachidonylglycerol and noladin ether, a novel putative endocannabinoid. Invest Ophthalmol Vis Sci 43 10 (2002) 3216-3222
208. Darmani N.A. Delta (9)-tetrahydrocannabinol and synthetic cannabinoids prevent emesis produced by the cannabinoid CB (1) receptor antagonist/inverse agonist SR 141716A. Neuropsychopharmacology 24 2 (2001) 198-203
209. Darmani N.A. The potent emetogenic effects of the endocannabinoid, 2-AG (2-arachidonoylglycerol) are blocked by delta (9)-tetrahydrocannabinol and other cannnabinoids. J Pharmacol Exp Ther 300 1 (2002) 34-42
210. Schlosburg J.E., Kinsey S.G., and Lichtman A.H. Targeting fatty acid amide hydrolase (FAAH) to treat pain and inflammation. AAPS J 11 1 (2009) 39-44
211. Leweke F.M., and Koethe D. Cannabis and psychiatric disorders: it is not only addiction. Addict Biol 13 2 (2008) 264-275
212. Bisogno T., and Di Marzo V. The role of the endocannabinoid system in Alzheimer's disease: facts and hypotheses. Curr Pharm Des 14 23 (2008) 2299-3305
213. Hermann H., Marsicano G., and Lutz B. Coexpression of the cannabinoid receptor type 1 with dopamine and serotonin receptors in distinct neuronal subpopulations of the adult mouse forebrain. Neuroscience 109 3 (2002) 451-460
214. Hohmann A.G., and Herkenham M. Localization of cannabinoid CB (1) receptor mRNA in neuronal subpopulations of rat striatum: a double-label in situ hybridization study. Synapse 37 1 (2000) 71-80
215. Cadogan A.K., Alexander S.P., Boyd E.A., and Kendall D.A. Influence of cannabinoids on electrically evoked dopamine release and cyclic AMP generation in the rat striatum. J Neurochem 69 3 (1997) 1131-1137
216. Solinas M., Justinova Z., Goldberg S.R., and Tanda G. Anandamide administration alone and after inhibition of fatty acid amide hydrolase (FAAH) increases dopamine levels in the nucleus accumbens shell in rats. J Neurochem 98 2 (2006) 408-419
217. Cheer J.F., Wassum K.M., Heien M.L.A.V., Phillips P.E.M., and Wightman R.M. Cannabinoids enhance subsecond dopamine release in the nucleus accumbens of awake rats. J Neurosci 24 (2004) 4393-4400
218. Giuffrida A., Parsons L.H., Kerr T.M., Rodriguez de Fonseca F., Navarro M., and Piomelli D. Dopamine activation of endogenous cannabinoid signaling in dorsal striatum. Nat Neurosci 2 4 (1999) 358-363
219. Ferrer B., Asbrock N., Kathuria S., Piomelli D., and Giuffrida A. Effects of levodopa on endocannabinoid levels in rat basal ganglia: implications for the treatment of levodopa-induced dyskinesias. Eur J Neurosci 18 6 (2003) 1607-1614
220. Masserano J.M., Karoum F., and Wyatt R.J. SR 141716A, a CB1 cannabinoid receptor antagonist, potentiates the locomotor stimulant effects of amphetamine and apomorphine. Behav Pharmacol 10 4 (1999) 429-432
221. Beltramo M., de Fonseca F.R., Navarro M., et al. Reversal of dopamine D (2) receptor responses by an anandamide transport inhibitor. J Neurosci 20 9 (2000) 3401-3407
222. Lastres-Becker I., Cebeira M., de Ceballos M., et al. Increased cannabinoid CB1 receptor binding and activation of GTP-binding proteins in the basal ganglia of patients with Parkinson's disease and MPTP-treated marmosets. Eur J Neurosci 14 (2001) 1827-1832
223. Romero J., Berrendero F., Perez-Rosado A., et al. Unilateral 6-hydroxydopamine lesions of nigrostriatal dopaminergic neurons increased CB1 receptor mRNA levels in the caudate-putamen. Life Sci 66 (2000) 485-494
224. Di Marzo V., Hill M.P., Bisogno T., Crossman A.R., and Brotchie J.M. Enhanced levels of endogenous cannabinoids in the globus pallidus are associated with a reduction in movement in an animal model of Parkinson's disease. FASEB J 14 (2000) 1432-1438
225. Gubellini P., Picconi B., Bari M., et al. Experimental parkinsonism alters endocannabinoid degradation: implications for striatal glutamatergic transmission. J Neurosci 22 (2002) 6900-6907
226. Kreitzer A.C., and Malenka R.C. Endocannabinoid-mediated rescue of striatal LTD and motor deficits in Parkinson's disease models. Nature 445 7128 (2007) 643-647
227. Zeng B.Y., Dass B., Owen A., et al. Chronic L-DOPA treatment increases striatal cannabinoid CB1 receptor mRNA expression in 6-hydroxydopamine-lesioned rats. Neurosci Lett 276 (1999) 71-74
228. Meschler J.P., Howlett A.C., and Madras B.K. Cannabinoid receptor agonist and antagonist effects on motor function in normal and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)-treated non-human primates. Psychopharmacology (Berl) 156 1 (2001) 79-85
229. Mesnage V., Houeto J.L., Bonnet A.M., et al. Neurokinin B, neurotensin, and cannabinoid receptor antagonists and Parkinson disease. Clin Neuropharmacol 27 3 (2004) 108-110
230. van der Stelt M., Fox S.H., Hill M., et al. A role for endocannabinoids in the generation of parkinsonism and levodopa-induced dyskinesia in MPTP-lesioned non-human primate models of Parkinson's disease. FASEB J 19 9 (2005) 1140-1142
231. Cao X., Liang L., Hadcock J.R., et al. Blockade of cannabinoid type 1 receptors augments the antiparkinsonian action of levodopa without affecting dyskinesias in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated rhesus monkeys. J Pharmacol Exp Ther 323 1 (2007) 318-326
232. Papa S.M. The cannabinoid system in Parkinson's disease: multiple targets to motor effects. Exp Neurol 211 2 (2008) 334-338
233. Obeso J.A., Rodriguez-Oroz M., Marin C., et al. The origin of motor fluctuations in Parkinson's disease: importance of dopaminergic innervation and basal ganglia circuits. Neurology 62 1 Suppl. 1 (2004) S17-S30
234. Sieradzan K.A., Fox S.H., Hill M., Dick J.P., Crossman A.R., and Brotchie J.M. Cannabinoids reduce levodopa-induced dyskinesia in Parkinson's disease: a pilot study. Neurology 57 11 (2001) 2108-2111
235. Gerdeman G.L., Ronesi J., and Lovinger D.M. Postsynaptic endocannabinoid release is critical to long-term depression in the striatum. Nat Neurosci 5 (2002) 446-451
236. Picconi B., Centonze D., Hakansson K., et al. Loss of bidirectional striatal synaptic plasticity in L-DOPA-induced dyskinesia. Nat Neurosci 6 (2003) 501-506
237. Carroll C.B., Bain P.G., Teare L., et al. Cannabis for dyskinesia in Parkinson disease. Neurology 63 (2004) 1245-1250
238. Vitale C., Pellecchia M.T., Grossi D., et al. Unawareness of dyskinesias in Parkinson's and Huntington's diseases. Neurol Sci 22 1 (2001) 105-106
239. Tzavara E.T., Li D.L., Moutsimilli L., et al. Endocannabinoids activate transient receptor potential vanilloid 1 receptors to reduce hyperdopaminergia-related hyperactivity: therapeutic implications. Biol Psychiatry 59 6 (2006) 508-515
240. Lastres-Becker I., de Miguel R., De Petrocellis L., Makriyannis A., Di Marzo V., and Fernandez-Ruiz J. Compounds acting at the endocannabinoid and/or endovanilloid systems reduce hyperkinesia in a rat model of Huntington's disease. J Neurochem 84 5 (2003) 1097-1109
241. Lee J., Di Marzo V., and Brotchie J.M. A role for vanilloid receptor 1 (TRPV1) and endocannabinnoid signalling in the regulation of spontaneous and L-DOPA induced locomotion in normal and reserpine-treated rats. Neuropharmacology 51 3 (2006) 557-565
242. Cenci M.A., Whishaw I.Q., and Schallert T. Animal models of neurological deficits: how relevant is the rat?. Nat Rev Neurosci 3 (2002) 574-579
243. Beardsley P.M., and Thomas B.F. Current evidence supporting a role of cannabinoid CB1 receptor (CB1R) antagonists as potential pharmacotherapies for drug abuse disorders. Behav Pharmacol 16 5-6 (2005) 275-296
244. Ator N.A., and Griffiths R.R. Principles of drug abuse liability assessment in laboratory animals. Drug Alcohol Depend 70 3 Suppl. (2003) S55-S72
245. Tzschentke T.M. Measuring reward with the conditioned place preference (CPP) paradigm: update of the last decade. Addict Biol 12 3-4 (2007) 227-462
246. Epstein D.H., Preston K.L., Stewart J., and Shaham Y. Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure. Psychopharmacology (Berl) 189 1 (2006) 1-16
247. Katz J.L., and Higgins S.T. The validity of the reinstatement model of craving and relapse to drug use. Psychopharmacology (Berl) 168 1-2 (2003) 21-30
248. Justinova Z., Goldberg S.R., Heishman S.J., and Tanda G. Self-administration of cannabinoids by experimental animals and human marijuana smokers. Pharmacol Biochem Behav 81 2 (2005) 285-299
249. Cheer J.F., Kendall D.A., and Marsden C.A. Cannabinoid receptors and reward in the rat: a conditioned place preference study. Psychopharmacology (Berl) 151 1 (2000) 25-30
250. Tanda G., Munzar P., and Goldberg S.R. Self-administration behavior is maintained by the psychoactive ingredient of marijuana in squirrel monkeys. Nat Neurosci 3 11 (2000) 1073-1074
251. Justinova Z., Tanda G., Redhi G.H., and Goldberg S.R. Self-administration of delta9-tetrahydrocannabinol (THC) by drug naive squirrel monkeys. Psychopharmacology (Berl) 169 2 (2003) 135-140
252. Justinova Z., Solinas M., Tanda G., Redhi G.H., and Goldberg S.R. The endogenous cannabinoid anandamide and its synthetic analog R (+)-methanandamide are intravenously self-administered by squirrel monkeys. J Neurosci 25 23 (2005) 5645-5650
253. Vlachou S., Nomikos G.G., and Panagis G. Effects of endocannabinoid neurotransmission modulators on brain stimulation reward. Psychopharmacology (Berl) 188 3 (2006) 293-305
254. Colombo G., Serra S., Brunetti G., et al. Stimulation of voluntary ethanol intake by cannabinoid receptor agonists in ethanol-preferring sP rats. Psychopharmacology (Berl) 159 2 (2002) 181-187
255. Gallate J.E., Saharov T., Mallet P.E., and McGregor I.S. Increased motivation for beer in rats following administration of a cannabinoid CB1 receptor agonist. Eur J Pharmacol 370 3 (1999) 233-240
256. McGregor I.S., Dam K.D., Mallet P.E., and Gallate J.E. Delta9-THC reinstates beer- and sucrose-seeking behaviour in abstinent rats: comparison with midazolam, food deprivation and predator odour. Alcohol Alcohol 40 1 (2005) 35-45
257. Solinas M., Panlilio L.V., Tanda G., Makriyannis A., Matthews S.A., and Goldberg S.R. Cannabinoid agonists but not inhibitors of endogenous cannabinoid transport or metabolism enhance the reinforcing efficacy of heroin in rats. Neuropsychopharmacology 30 11 (2005) 2046-2057
258. Cippitelli A., Cannella N., Braconi S., et al. Increase of brain endocannabinoid anandamide levels by FAAH inhibition and alcohol abuse behaviours in the rat. Psychopharmacology (Berl) 198 4 (2008) 449-460
259. Basavarajappa B.S., Yalamanchili R., Cravatt B.F., Cooper T.B., and Hungund B.L. Increased ethanol consumption and preference and decreased ethanol sensitivity in female FAAH knockout mice. Neuropharmacology 50 7 (2006) 834-844
260. Blednov Y.A., Cravatt B.F., Boehm II S.L., Walker D., and Harris R.A. Role of endocannabinoids in alcohol consumption and intoxication: studies of mice lacking fatty acid amide hydrolase. Neuropsychopharmacology 32 7 (2007) 1570-1582
261. Vinod K.Y., Sanguino E., Yalamanchili R., Manzanares J., and Hungund B.L. Manipulation of fatty acid amide hydrolase functional activity alters sensitivity and dependence to ethanol. J Neurochem 104 1 (2008) 233-243
262. Scherma M., Panlilio L.V., Fadda P., et al. Inhibition of anandamide hydrolysis by cyclohexyl carbamic acid 3'-carbamoyl-3-yl ester (URB597) reverses abuse-related behavioral and neurochemical effects of nicotine in rats. J Pharmacol Exp Ther 327 2 (2008) 482-490
263. Corrigall W.A., Franklin K.B., Coen K.M., and Clarke P.B. The mesolimbic dopaminergic system is implicated in the reinforcing effects of nicotine. Psychopharmacology (Berl) 107 2-3 (1992) 285-289
264. Merritt L.L., Martin B.R., Walters C., Lichtman A.H., and Damaj M.I. The endogenous cannabinoid system modulates nicotine reward and dependence. J Pharmacol Exp Ther 326 2 (2008) 483-492
265. Price D., Martinez A.A., Seillier A., and Koek W. WIN55,212-2, a cannabinoid receptor agonist, protects against nigrostriatal cell loss in the MPTP mouse model of Parkinson's disease. Eur J Neurosci (2009) 10.1111/j.1460-9568.2009.06764.x
266. Iuvone T., Esposito G., De Filippis D., and Bisogno T. Cannabinoid CB1 receptor stimulation affords neuroprotection in MPTP-induced neurotoxicity by attenuating S100B up-regulation in vitro. J Mol Med 85 (2007) 1379-1392
267. Lastres-Becker I., Molina-Holgado E., Ramos J.A., and Mechoulam R. Cannabinoids provide neuroprotection against 6-hydroxydopamine toxicity in vivo and in vitro: relevance to Parkinson's disease. Neurobiol Dis 19 (2005) 96-107