Opposing local effects of endocannabinoids on the activity of noradrenergic neurons and release of noradrenaline: Relevance for their role in depression and in the actions of CB1 receptor antagonists

Journal of Neural Transmission

Volumn 120, Issue 1, 2013, Pages 177-186

  Kirilly, E ^a   Hunyady, L ^a   Bagdy, G ^a  

^a SEMMELWEIS UNIVERSITY   (Hungary)

Author keywords

Antidepressants; Anxiety; CB1 receptor; Depression; Endocannabinoids; GABA; Glutamate; Locus Coeruleus; Non CB1 endocannabinoid receptor; Noradrenaline; Serotonin

Indexed keywords

2 ARACHIDONOYLGLYCEROL; ALPHA 1 ADRENERGIC RECEPTOR; ANANDAMIDE; BETA 1 ADRENERGIC RECEPTOR; CALCIUM; CANNABINOID 1 RECEPTOR ANTAGONIST; CANNABINOID 2 RECEPTOR; ENDOCANNABINOID; N METHYL DEXTRO ASPARTIC ACID; NORADRENALIN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; SEROTONIN; VANILLOID RECEPTOR;

CALCIUM SIGNALING; DEPRESSION; DRUG EFFECT; ENZYME ACTIVATION; LATERAL TEGMENTUM; LOCUS CERULEUS; NEUROTRANSMISSION; NORADRENALIN RELEASE; NORADRENERGIC NERVE; PRIORITY JOURNAL; PROTEIN INTERACTION; PROTEIN LOCALIZATION; REGULATORY MECHANISM; REVIEW; TEGMENTUM;

ADRENERGIC NEURONS; DEPRESSION; ENDOCANNABINOIDS; HUMANS; LOCUS COERULEUS; MODELS, BIOLOGICAL; NOREPINEPHRINE; RECEPTOR, CANNABINOID, CB1;

EID: 84872350576     PISSN: 03009564     EISSN: 14351463     Source Type: Journal    
DOI: 10.1007/s00702-012-0900-1     Document Type: Review

References (132)

1. Adermark L, Lovinger DM (2007) Retrograde endocannabinoid signaling at striatal synapses requires a regulated postsynaptic release step. Proc Natl Acad Sci USA 104(51):20564-20569
2. Aghajanian GK, Cedarbaum JM, Wang RY (1977) Evidence for norepinephrine-mediated collateral inhibition of locus coeruleus neurons. Brain Res 136(3):570-577 (Pubitemid 8228265)
3. Anand A, Charney DS (2000) Norepinephrine dysfunction in depression. J Clin Psychiatry 61(Suppl 10):16-24 (Pubitemid 30485421)
4. Arborelius L, Owens MJ, Plotsky PM, Nemeroff CB (1999) The role of corticotropin-releasing factor in depression and anxiety disorders. J Endocrinol 160(1):1-12 (Pubitemid 29044562)
5. Ashton CH, Moore PB (2011) Endocannabinoid system dysfunction in mood and related disorders. Acta Psychiatr Scand 124(4):250-261
6. Aso E, Renoir T, Mengod G, Ledent C, Hamon M, Maldonado R, Lanfumey L, Valverde O (2009) Lack of CB1 receptor activity impairs serotonergic negative feedback. J Neurochem 109(3):935-944
7. Aston-Jones G, Shipley MT, Chouvet G, Ennis M, van Bockstaele E, Pieribone V, Shiekhattar R, Akaoka H, Drolet G, Astier B et al (1991) Afferent regulation of locus coeruleus neurons: anatomy, physiology and pharmacology. Prog Brain Res 88:47-75
8. Bagdy G (1998) Serotonin, anxiety, and stress hormones. Focus on 5-HT receptor subtypes, species and gender differences. Ann N Y Acad Sci 851:357-363 (Pubitemid 28370396)
9. Balazsa T, Biro J, Gullai N, Ledent C, Sperlagh B (2008) CB1-cannabinoid receptors are involved in the modulation of non-synaptic [3H]serotonin release from the rat hippocampus. Neurochem Int 52(1-2):95-102 (Pubitemid 350235715)
10. Baldwin DS, Evans DL, Hirschfeld RM, Kasper S (2002) Can we distinguish anxiety from depression? Psychopharmacol Bull 36(Suppl 2):158-165
11. Bambico FR, Katz N, Debonnel G, Gobbi G (2007) Cannabinoids elicit antidepressant-like behavior and activate serotonergic neurons through the medial prefrontal cortex. J Neurosci 27(43):11700-11711 (Pubitemid 350006914)
12. Bambico FR, Duranti A, Tontini A, Tarzia G, Gobbi G (2009) Endocannabinoids in the treatment of mood disorders: evidence from animal models. Curr Pharm Des 15(14):1623-1646
13. Barna I, Zelena D, Arszovszki AC, Ledent C (2004) The role of endogenous cannabinoids in the hypothalamo-pituitary-adrenal axis regulation: in vivo and in vitro studies in CB1 receptor knockout mice. Life Sci 75(24):2959-2970 (Pubitemid 39349260)
14. Berridge CW, Waterhouse BD (2003) The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes. Brain Res Brain Res Rev 42(1):33-84 (Pubitemid 36369264)
15. Bertolino M, Vicini S, Gillis R, Travagli A (1997) Presynaptic alpha2-adrenoceptors inhibit excitatory synaptic transmission in rat brain stem. Am J Physiol 272(3 Pt 1):G654-G661
16. Blier P, Briley M (2011) The noradrenergic symptom cluster: clinical expression and neuropharmacology. Neuropsychiatr Dis Treat 7(Suppl 1):15-20
17. Boehm S (1999) Presynaptic alpha2-adrenoceptors control excitatory, but not inhibitory, transmission at rat hippocampal synapses. J Physiol 519(Pt 2):439-449 (Pubitemid 29430007)
18. Brunello N, Mendlewicz J, Kasper S, Leonard B, Montgomery S, Nelson J, Paykel E, Versiani M, Racagni G (2002) The role of noradrenaline and selective noradrenaline reuptake inhibition in depression. Eur Neuropsychopharmacol 12(5):461-475
19. Buffalari DM, Grace AA (2007) Noradrenergic modulation of basolateral amygdala neuronal activity: opposing influences of alpha-2 and beta receptor activation. J Neurosci 27(45):12358-12366 (Pubitemid 350085480)
20. Carvalho AF, Mackie K, Van Bockstaele EJ (2010) Cannabinoid modulation of limbic forebrain noradrenergic circuitry. Eur J Neurosci 31(2):286-301
21. Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301(5631):386-389 (Pubitemid 36877077)
22. Caspi A, Hariri AR, Holmes A, Uher R, Moffitt TE (2010) Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits. Am J Psychiatry 167(5):509-527
23. Cedarbaum JM, Aghajanian GK (1977) Catecholamine receptors on locus coeruleus neurons: pharmacological characterization. Eur J Pharmacol 44(4):375-385 (Pubitemid 8160203)
24. Celada P, Puig M, Amargos-Bosch M, Adell A, Artigas F (2004) The therapeutic role of 5-HT1A and 5-HT2A receptors in depression. J Psychiatry Neurosci 29(4):252-265 (Pubitemid 39185866)
25. Christensen NJ, Vestergaard P, Sorensen T, Jerris AG, Rafaelsen OJ (1980) Cerebrospinal fluid adrenaline in endogenous depression. Lancet 1(8170):722
26. Christensen R, Kristensen PK, Bartels EM, Bliddal H, Astrup A (2007) Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials. Lancet 370(9600):1706-1713 (Pubitemid 350100788)
27. Cota D, Steiner MA, Marsicano G, Cervino C, Herman JP, Grubler Y, Stalla J, Pasquali R, Lutz B, Stalla GK, Pagotto U (2007) Requirement of cannabinoid receptor type 1 for the basal modulation of hypothalamic-pituitary-adrenal axis function. Endocrinology 148(4):1574-1581 (Pubitemid 46457104)
28. Dahlstrom A, Fuxe K (1964) Localization of monoamines in the lower brain stem. Experientia 20(7):398-399
29. De Paermentier F, Cheetham SC, Crompton MR, Katona CL, Horton RW (1991) Brain beta-adrenoceptor binding sites in depressed suicide victims: effects of antidepressant treatment. Psychopharmacology 105(2):283-288
30. De Paermentier F, Mauger JM, Lowther S, Crompton MR, Katona CL, Horton RW (1997) Brain alpha-adrenoceptors in depressed suicides. Brain Res 757(1):60-68 (Pubitemid 27244621)
31. Delgado PL (2000) Depression: the case for a monoamine deficiency. J Clin Psychiatry 61(Suppl 6):7-11 (Pubitemid 30217405)
32. Delgado PL, Moreno FA (2000) Role of norepinephrine in depression. J Clin Psychiatry 61(Suppl 1):5-12 (Pubitemid 30124144)
33. Dell'Osso B, Palazzo MC, Oldani L, Altamura AC (2011) The noradrenergic action in antidepressant treatments: pharmacological and clinical aspects. CNS Neurosci Ther 17(6):723-732
34. Denson TF, Earleywine M (2006) Decreased depression in marijuana users. Addict Behav 31(4):738-742
35. Despres JP (2009) Pleiotropic effects of rimonabant: clinical implications. Curr Pharm Des 15(5):553-570
36. Despres JP, Golay A, Sjostrom L (2005) Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med 353(20):2121-2134 (Pubitemid 41653104)
37. Domschke K, Dannlowski U, Ohrmann P, Lawford B, Bauer J, Kugel H, Heindel W, Young R, Morris P, Arolt V, Deckert J, Suslow T, Baune BT (2008) Cannabinoid receptor 1 (CNR1) gene: impact on antidepressant treatment response and emotion processing in major depression. Eur Neuropsychopharmacol 18(10):751-759
38. Drevets WC (2001) Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders. Curr Opin Neurobiol 11(2):240-249 (Pubitemid 32289413)
39. Duman RS, Monteggia LM (2006) A neurotrophic model for stress-related mood disorders. Biol Psychiatry 59(12):1116-1127
40. FDA (2007) US Food and Drug Administration Advisory Committee. FDA briefi ng document: zimulti (rimonabant) Tablets, 20 mg http://www.fda.gov/OHRMS/ DOCKETS/AC/07/briefing/2007-4306b1-00-index.htm. Assessed Aug 6 2007
41. Filakovszky J, Gerber K, Bagdy G (1999) A serotonin-1A receptor agonist and an N-methyl-D-aspartate receptor antagonist oppose each others effects in a genetic rat epilepsy model. Neurosci Lett 261(1-2):89-92 (Pubitemid 29100083)
42. Freund TF, Katona I, Piomelli D (2003) Role of endogenous cannabinoids in synaptic signaling. Physiol Rev 83(3):1017-1066 (Pubitemid 36828930)
43. Froger N, Gardier AM, Moratalla R, Alberti I, Lena I, Boni C, De Felipe C, Rupniak NM, Hunt SP, Jacquot C, Hamon M, Lanfumey L (2001) 5-hydroxytryptamine (5-HT)1A autoreceptor adaptive changes in substance P (neurokinin 1) receptor knock-out mice mimic antidepressant-induced desensitization. J Neurosci 21(20):8188-8197 (Pubitemid 32952774)
44. Gjerris A (1988) Baseline studies on transmitter substances in cerebrospinal fluid in depression. Acta Psychiatr Scand Suppl 346:1-35 (Pubitemid 19026910)
45. Gonda X, Rihmer Z, Juhasz G, Zsombok T, Bagdy G (2007) High anxiety and migraine are associated with the s allele of the 5HTTLPR gene polymorphism. Psychiatry Res 149(1-3):261-266 (Pubitemid 46108113)
46. Gonda X, Fountoulakis KN, Juhasz G, Rihmer Z, Lazary J, Laszik A, Akiskal HS, Bagdy G (2009) Association of the s allele of the 5-HTTLPR with neuroticism-related traits and temperaments in a psychiatrically healthy population. Eur Arch Psychiatry Clin Neurosci 259(2):106-113
47. Graeff FG, Guimaraes FS, De Andrade TG, Deakin JF (1996) Role of 5-HT in stress, anxiety, and depression. Pharmacol Biochem Behav 54(1):129-141 (Pubitemid 26146666)
48. Graf M, Jakus R, Kantor S, Levay G, Bagdy G (2004) Selective 5-HT1A and 5-HT7 antagonists decrease epileptic activity in the WAG/Rij rat model of absence epilepsy. Neurosci Lett 359(1-2):45-48 (Pubitemid 38446635)
49. Gruber AJ, Pope HG Jr, Brown ME (1996) Do patients use marijuana as an antidepressant? Depression 4(2):77-80 (Pubitemid 27099514)
50. Gyombolai P, Pap D, Turu G, Catt KJ, Bagdy G, Hunyady L (2012) Regulation of endocannabinoid release by G proteins: a paracrine mechanism of G protein-coupled receptor action. Mol Cell Endocrinol 353(1-2):29-36
51. Haddjeri N, Blier P, de Montigny C (1998) Long-term antidepressant treatments result in a tonic activation of forebrain 5-HT1A receptors. J Neurosci 18(23):10150-10156 (Pubitemid 28543788)
52. Hajos N, Katona I, Naiem SS, MacKie K, Ledent C, Mody I, Freund TF (2000) Cannabinoids inhibit hippocampal GABAergic transmission and network oscillations. Eur J Neurosci 12(9):3239-3249
53. Halbach OvBu, Dermietzel R (eds) (2002) Neurotransmitters and neuromodulators: handbook of receptors and biological effects. Wiley-VCH, Weinheim
54. Haller J, Bakos N, Szirmay M, Ledent C, Freund TF (2002) The effects of genetic and pharmacological blockade of the CB1 cannabinoid receptor on anxiety. Eur J Neurosci 16(7):1395-1398 (Pubitemid 35340861)
55. Haring M, Marsicano G, Lutz B, Monory K (2007) Identification of the cannabinoid receptor type 1 in serotonergic cells of raphe nuclei in mice. Neuroscience 146(3):1212-1219 (Pubitemid 46694132)
56. Heimann AS, Gomes I, Dale CS, Pagano RL, Gupta A, de Souza LL, Luchessi AD, Castro LM, Giorgi R, Rioli V, Ferro ES, Devi LA (2007) Hemopressin is an inverse agonist of CB1 cannabinoid receptors. Proc Natl Acad Sci USA 104(51):20588-20593
57. Henstridge CM, Balenga NA, Kargl J, Andradas C, Brown AJ, Irving A, Sanchez C, Waldhoer M (2011) Minireview: recent developments in the physiology and pathology of the lysophosphatidylinositol-sensitive receptor GPR55. Mol Endocrinol 25(11):1835-1848
58. Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, de Costa BR, Rice KC (1990) Cannabinoid receptor localization in brain. Proc Natl Acad Sci USA 87(5):1932-1936
59. Herkenham M, Lynn AB, Johnson MR, Melvin LS, de Costa BR, Rice KC (1991) Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J Neurosci 11(2):563-583
60. Hill MN, Gorzalka BB (2005) Is there a role for the endocannabinoid system in the etiology and treatment of melancholic depression? Behav Pharmacol 16(5-6):333-352 (Pubitemid 41404805)
61. Hill MN, Carrier EJ, McLaughlin RJ, Morrish AC, Meier SE, Hillard CJ, Gorzalka BB (2008a) Regional alterations in the endocannabinoid system in an animal model of depression: effects of concurrent antidepressant treatment. J Neurochem 106(6):2322-2336
62. Hill MN, Miller GE, Ho WS, Gorzalka BB, Hillard CJ (2008b) Serum endocannabinoid content is altered in females with depressive disorders: a preliminary report. Pharmacopsychiatry 41(2):48-53 (Pubitemid 351427522)
63. Hill MN, Hillard CJ, Bambico FR, Patel S, Gorzalka BB, Gobbi G (2009a) The therapeutic potential of the endocannabinoid system for the development of a novel class of antidepressants. Trends Pharmacol Sci 30(9):484-493
64. Hill MN, Miller GE, Carrier EJ, Gorzalka BB, Hillard CJ (2009b) Circulating endocannabinoids and N-acyl ethanolamines are differentially regulated in major depression and following exposure to social stress. Psychoneuroendocrinology 34(8):1257-1262
65. Hirschfeld RM (2000) History and evolution of the monoamine hypothesis of depression. J Clin Psychiatry 61(Suppl 6):4-6 (Pubitemid 30217404)
66. Holsboer F (2000) The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 23(5):477-501
67. Irving AJ, Rae MG, Coutts AA (2002) Cannabinoids on the brain. ScientificWorldJournal 2:632-648
68. Juhasz G, Chase D, Pegg E, Downey D, Toth ZG, Stones K, Platt H, Mekli K, Payton A, Elliott R, Anderson IM, Deakin JF (2009) CNR1 gene is associated with high neuroticism and low agreeableness and interacts with recent negative life events to predict current depressive symptoms. Neuropsychopharmacology 34(8):2019-2027
69. Kahn RS, van Praag HM, Wetzler S, Asnis GM, Barr G (1988) Serotonin and anxiety revisited. Biol Psychiatry 23(2):189-208 (Pubitemid 18023098)
70. Kano M, Ohno-Shosaku T, Hashimotodani Y, Uchigashima M, Watanabe M (2009) Endocannabinoid-mediated control of synaptic transmission. Physiol Rev 89(1):309-380
71. Kantor S, Anheuer ZE, Bagdy G (2000) High social anxiety and low aggression in Fawn-Hooded rats. Physiol Behav 71(5):551-557 (Pubitemid 32184780)
72. Katona I, Urban GM, Wallace M, Ledent C, Jung KM, Piomelli D, Mackie K, Freund TF (2006) Molecular composition of the endocannabinoid system at glutamatergic synapses. J Neurosci 26(21):5628-5637 (Pubitemid 44315254)
73. Kaufman J, Charney D (2000) Comorbidity of mood and anxiety disorders. Depress Anxiety 12(Suppl 1):69-76
74. Kawamura Y, Fukaya M, Maejima T, Yoshida T, Miura E, Watanabe M, Ohno-Shosaku T, Kano M (2006) The CB1 cannabinoid receptor is the major cannabinoid receptor at excitatory presynaptic sites in the hippocampus and cerebellum. J Neurosci 26(11):2991-3001
75. Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS (2003) The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 289(23):3095-3105 (Pubitemid 37432885)
76. Kirilly E, Gonda X, Bagdy G (2012) CB1 receptor antagonists: new discoveries leading to new perspectives. Acta Physiol (Oxf) 205(1):41-60
77. Lauckner JE, Jensen JB, Chen HY, Lu HC, Hille B, Mackie K (2008) GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc Natl Acad Sci USA 105(7):2699-2704 (Pubitemid 351520576)
78. Lazary J, Lazary A, Gonda X, Benko A, Molnar E, Hunyady L, Juhasz G, Bagdy G (2009) Promoter variants of the cannabinoid receptor 1 gene (CNR1) in interaction with 5-HTTLPR affect the anxious phenotype. Am J Med Genet B Neuropsychiatr Genet 150B(8):1118-1127
79. Lazary J, Juhasz G, Hunyady L, Bagdy G (2011) Personalized medicine can pave the way for the safe use of CB(1) receptor antagonists. Trends Pharmacol Sci 32(5):270-280
80. Leonard BE (2000) Evidence for a biochemical lesion in depression. J Clin Psychiatry 61(Suppl 6):12-17 (Pubitemid 30217406)
81. Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, Benjamin J, Muller CR, Hamer DH, Murphy DL (1996) Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274(5292):1527-1531 (Pubitemid 26403928)
82. Lovinger DM, Davis MI, Costa RM (2010) Endocannabinoid signaling in the striatum. In: Steiner H, Tseng KY (eds) Handbook of basal ganglia structure and function. Academic Press, London, pp 167-186
83. Mackie K (2005) Distribution of cannabinoid receptors in the central and peripheral nervous system. Handb Exp Pharmacol 168:299-325
84. Maione S, Bisogno T, de Novellis V, Palazzo E, Cristino L, Valenti M, Petrosino S, Guglielmotti V, Rossi F, Di Marzo V (2006) 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):969-982 (Pubitemid 43345268)
85. Manta S, El Mansari M, Debonnel G, Blier P (2012) Electrophysiological and neurochemical effects of long-term vagus nerve stimulation on the rat monoaminergic systems. Int J Neuropsychopharmacol 17:1-12
86. Marsicano G, Lutz B (1999) Expression of the cannabinoid receptor CB1 in distinct neuronal subpopulations in the adult mouse forebrain. Eur J Neurosci 11(12):4213-4225 (Pubitemid 30009252)
87. Mato S, Aso E, Castro E, Martin M, Valverde O, Maldonado R, Pazos A (2007) CB1 knockout mice display impaired functionality of 5-HT1A and 5-HT2A/C receptors. J Neurochem 103(5):2111-2120 (Pubitemid 350126641)
88. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346(6284):561-564 (Pubitemid 20238806)
89. Matsuda LA, Bonner TI, Lolait SJ (1993) Localization of cannabinoid receptor mRNA in rat brain. J Comp Neurol 327(4):535-550 (Pubitemid 23033649)
90. McEwen BS (2005) Glucocorticoids, depression, and mood disorders: structural remodeling in the brain. Metabolism 54(5 Suppl 1):20-23 (Pubitemid 40546018)
91. Mendiguren A, Pineda J (2004) Cannabinoids enhance N-methyl-D-aspartate- induced excitation of locus coeruleus neurons by CB1 receptors in rat brain slices. Neurosci Lett 363(1):1-5 (Pubitemid 38639839)
92. Mendiguren A, Pineda J (2006) Systemic effect of cannabinoids on the spontaneous firing rate of locus coeruleus neurons in rats. Eur J Pharmacol 534(1-3):83-88 (Pubitemid 43384186)
93. Monory K, Massa F, Egertova M, Eder M, Blaudzun H, Westenbroek R, Kelsch W, Jacob W, Marsch R, Ekker M, Long J, Rubenstein JL, Goebbels S, Nave KA, During M, Klugmann M, Wolfel B, Dodt HU, Zieglgansberger W, Wotjak CT, Mackie K, Elphick MR, Marsicano G, Lutz B (2006) The endocannabinoid system controls key epileptogenic circuits in the hippocampus. Neuron 51(4):455-466 (Pubitemid 44209321)
94. Moore RY, Card JP (eds) (1984) Noradrenaline-containing neuron systems. Handbook of chemical neuroanatomy, vol 2. Elsevier, Amsterdam
95. Moreira FA, Crippa JA (2009) The psychiatric side-effects of rimonabant. Rev Bras Psiquiatr 31(2):145-153
96. Moretti A, Gorini A, Villa RF (2003) Affective disorders, antidepressant drugs and brain metabolism. Mol Psychiatry 8(9):773-785 (Pubitemid 37100711)
97. Muntoni AL, Pillolla G, Melis M, Perra S, Gessa GL, Pistis M (2006) Cannabinoids modulate spontaneous neuronal activity and evoked inhibition of locus coeruleus noradrenergic neurons. Eur J Neurosci 23(9):2385-2394 (Pubitemid 43742870)
98. Nutt DJ (2002) The neuropharmacology of serotonin and noradrenaline in depression. Int Clin Psychopharmacol 17(Suppl 1):S1-S12
99. O'Brien JT, Ames D, Schweitzer I, Colman P, Desmond P, Tress B (1996) Clinical and magnetic resonance imaging correlates of hypothalamic-pituitary- adrenal axis function in depression and Alzheimer's disease. Br J Psychiatry 168(6):679-687
100. Olpe HR, Steinmann M (1991) Responses of locus coeruleus neurons to neuropeptides. Prog Brain Res 88:241-248
101. Onaivi ES, Ishiguro H, Gong JP, Patel S, Perchuk A, Meozzi PA, Myers L, Mora Z, Tagliaferro P, Gardner E, Brusco A, Akinshola BE, Liu QR, Hope B, Iwasaki S, Arinami T, Teasenfitz L, Uhl GR (2006) Discovery of the presence and functional expression of cannabinoid CB2 receptors in brain. Ann N Y Acad Sci 1074:514-536 (Pubitemid 44532857)
102. Oropeza VC, Mackie K, Van Bockstaele EJ (2007) Cannabinoid receptors are localized to noradrenergic axon terminals in the rat frontal cortex. Brain Res 1127(1):36-44 (Pubitemid 44854843)
103. Owens MJ, Nemeroff CB (1994) Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. Clin Chem 40(2):288-295 (Pubitemid 24072594)
104. Patel S, Roelke CT, Rademacher DJ, Cullinan WE, Hillard CJ (2004) Endocannabinoid signaling negatively modulates stress-induced activation of the hypothalamic-pituitary-adrenal axis. Endocrinology 145(12):5431-5438 (Pubitemid 39564580)
105. Penninx BW, Beekman AT, Bandinelli S, Corsi AM, Bremmer M, Hoogendijk WJ, Guralnik JM, Ferrucci L (2007) Late-life depressive symptoms are associated with both hyperactivity and hypoactivity of the hypothalamo-pituitary-adrenal axis. Am J Geriatr Psychiatry 15(6):522-529
106. Pistis M, Perra S, Pillolla G, Melis M, Gessa GL, Muntoni AL (2004) Cannabinoids modulate neuronal firing in the rat basolateral amygdala: evidence for CB1- and non-CB1-mediated actions. Neuropharmacology 46(1):115-125 (Pubitemid 37494745)
107. Poddar MK, Dewey WL (1980) Effects of cannabinoids on catecholamine uptake and release in hypothalamic and striatal synaptosomes. J Pharmacol Exp Ther 214(1):63-67 (Pubitemid 10032383)
108. Reguero L, Puente N, Elezgarai I, Mendizabal-Zubiaga J, Canduela MJ, Buceta I, Ramos A, Suarez J, Rodriguez de Fonseca F, Marsicano G, Grandes P (2011) GABAergic and cortical and subcortical glutamatergic axon terminals contain CB1 cannabinoid receptors in the ventromedial nucleus of the hypothalamus. PLoS One 6(10):e26167
109. Ressler KJ, Nemeroff CB (2000) Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depress Anxiety 12(Suppl 1):2-19
110. Ruilope LM, Despres JP, Scheen A, Pi-Sunyer X, Mancia G, Zanchetti A, Van Gaal L (2008) Effect of rimonabant on blood pressure in overweight/obese patients with/without co-morbidities: analysis of pooled RIO study results. J Hypertens 26(2):357-367
111. Ryberg E, Larsson N, Sjogren S, Hjorth S, Hermansson NO, Leonova J, Elebring T, Nilsson K, Drmota T, Greasley PJ (2007) The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol 152(7):1092-1101 (Pubitemid 350166046)
112. Samuels ER, Szabadi E (2008) Functional neuroanatomy of the noradrenergic locus coeruleus: its roles in the regulation of arousal and autonomic function part I: principles of functional organisation. Curr Neuropharmacol 6(3):235-253
113. Schildkraut JJ (1965) The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am J Psychiatry 122(5):509-522
114. Stanley M, Mann JJ (1983) Increased serotonin-2 binding sites in frontal cortex of suicide victims. Lancet 1(8318):214-216 (Pubitemid 13171106)
115. Suarez J, Bermudez-Silva FJ, Mackie K, Ledent C, Zimmer A, Cravatt BF, de Fonseca FR (2008) Immunohistochemical description of the endogenous cannabinoid system in the rat cerebellum and functionally related nuclei. J Comp Neurol 509(4):400-421
116. Szemeredi K, Komoly S, Kopin IJ, Bagdy G, Keiser HR, Goldstein DS (1991) Simultaneous measurement of plasma and brain extracellular fluid concentrations of catechols after yohimbine administration in rats. Brain Res 542(1):8-14
117. Tanimura A, Yamazaki M, Hashimotodani Y, Uchigashima M, Kawata S, Abe M, Kita Y, Hashimoto K, Shimizu T, Watanabe M, Sakimura K, Kano M (2010) The endocannabinoid 2-arachidonoylglycerol produced by diacylglycerol lipase alpha mediates retrograde suppression of synaptic transmission. Neuron 65(3):320-327
118. To CT, Bagdy G (1999) Anxiogenic effect of central CCK administration is attenuated by chronic fluoxetine or ipsapirone treatment. Neuropharmacology 38(2):279-282 (Pubitemid 29073548)
119. Tsigos C, Chrousos GP (2002) Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res 53(4):865-871 (Pubitemid 35282615)
120. Tsou K, Brown S, Sanudo-Pena MC, Mackie K, Walker JM (1998) Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neuroscience 83(2):393-411 (Pubitemid 28062631)
121. Turu G, Simon A, Gyombolai P, Szidonya L, Bagdy G, Lenkei Z, Hunyady L (2007) The role of diacylglycerol lipase in constitutive and angiotensin AT1 receptor-stimulated cannabinoid CB1 receptor activity. J Biol Chem 282(11):7753-7757 (Pubitemid 47093542)
122. Turu G, Varnai P, Gyombolai P, Szidonya L, Offertaler L, Bagdy G, Kunos G, Hunyady L (2009) Paracrine transactivation of the CB1 cannabinoid receptor by AT1 angiotensin and other Gq/11 protein-coupled receptors. J Biol Chem 284(25):16914-16921
123. Umathe SN, Manna SS, Jain NS (2011) Involvement of endocannabinoids in antidepressant and anti-compulsive effect of fluoxetine in mice. Behav Brain Res 223(1):125-134
124. Valverde O, Torrens M (2012) CB1 receptor-deficient mice as a model for depression. Neuroscience 204:193-206
125. Van Gaal L, Pi-Sunyer X, Despres JP, McCarthy C, Scheen A (2008) Efficacy and safety of rimonabant for improvement of multiple cardiometabolic risk factors in overweight/obese patients: pooled 1-year data from the rimonabant in obesity (RIO) program. Diabetes Care 31(Suppl 2):S229-S240
126. Van Waes V, Beverley JA, Siman H, Tseng KY, Steiner H (2012) CB1 cannabinoid receptor expression in the striatum: association with corticostriatal circuits and developmental regulation. Front Pharmacol 3:21
127. Viveros MP, Marco EM, File SE (2005) Endocannabinoid system and stress and anxiety responses. Pharmacol Biochem Behav 81(2):331-342 (Pubitemid 40807131)
128. Weiss JM, Stout JC, Aaron MF, Quan N, Owens MJ, Butler PD, Nemeroff CB (1994) Depression and anxiety: role of the locus coeruleus and corticotropin-releasing factor. Brain Res Bull 35(5-6):561-572
129. WHO (2011) Depression. http://www.who.int/mental-health/management/ depression/definition/en/
130. Williamson EM, Evans FJ (2000) Cannabinoids in clinical practice. Drugs 60(6):1303-1314 (Pubitemid 32039388)
131. Wittchen HU, Kessler RC, Pfister H, Lieb M (2000) Why do people with anxiety disorders become depressed? A prospective-longitudinal community study. Acta Psychiatr Scand Suppl 406:14-23
132. Yates M, Leake A, Candy JM, Fairbairn AF, McKeith IG, Ferrier IN (1990) 5HT2 receptor changes in major depression. Biol Psychiatry 27(5):489-496 (Pubitemid 20091992)