Hub and switches: Endocannabinoid signalling in midbrain dopamine neurons

Philosophical Transactions of the Royal Society B: Biological Sciences

Volumn 367, Issue 1607, 2012, Pages 3276-3285

  Melis, Miriam ^a   Pistis, Marco ^a  

^a UNIVERSITY OF CAGLIARI   (Italy)

Author keywords

Addiction; Dopamine neurons; Endocannabinoids; Peroxisome proliferator activated receptors; Reward; Rodent

Indexed keywords

EID: 84868159290     PISSN: 09628436     EISSN: 14712970     Source Type: Journal    
DOI: 10.1098/rstb.2011.0383     Document Type: Review

References (116)

1. Björklund, A. & Dunnett, S. B. 2007 Dopamine neuron systems in the brain: an update. Trends Neurosci. 30, 194-202. (doi:10.1016/j.tins.2007.03.006)
2. Ungerstedt, U. 1971 Stereotaxic mapping of the monoamine pathways in the rat brain. Acta Physiol. Scand. Suppl. 367, 1-48.
3. Wise, R.A. 2009 Roles for nigrostriatal-not justmesocorticolimbic- dopamine in reward and addiction. Trends Neurosci. 32, 517-524. (doi:10.1016/j.tins.2009.06.004)
4. Margolis, E. B., Lock, H., Hjelmstad, G. O. & Fields, H. L. 2006 The ventral tegmental area revisited: is there an electrophysiological marker for dopaminergic neurons? J. Physiol. 577, 907-924. (doi:10.1113/jphysiol.2006.117069)
5. Yamaguchi, T., Wang, H. L., Li, X., Ng, T. H. & Morales, M. 2011 Mesocorticolimbic glutamatergic pathway. J. Neurosci. 31, 8476-8490. (doi:10.1523/JNEUROSCI.1598-11.2011)
6. Yamaguchi, T., Sheen, W. & Morales, M. 2007 Glutamatergic neurons are present in the rat ventral tegmental area. Eur. J. Neurosci. 25, 106-118. (doi:10.1111/j.1460-9568.2006.05263.x)
7. Beckstead, R. M., Domesick, V. B. & Nauta, W. J. 1979 Efferent connections of the substantia nigra and ventral tegmental area in the rat. Brain Res. 175, 191-217. (doi:10.1016/0006-8993(79)91001-1)
8. Fallon, J. H. & Moore, R. Y. 1978 Catecholamine innervation of the basal forebrain. IV. Topography of the dopamine projection to the basal forebrain and neostriatum. J. Comp. Neurol. 180, 545-580. (doi:10.1002/cne.901800310)
9. Ikemoto, S. 2010 Brain reward circuitry beyond the mesolimbic dopamine system: a neurobiological theory. Neurosci. Biobehav. Rev. 35, 129-150. (doi:10.1016/j.neubiorev.2010.02.001)
10. Jhou, T. C., Geisler, S., Marinelli, M., Degarmo, B. A. & Zahm, D. S. 2009 The mesopontine rostromedial tegmental nucleus: a structure targeted by the lateral habenula that projects to the ventral tegmental area of Tsai and substantia nigra compacta. J. Comp. Neurol. 513, 566-596. (doi:10.1002/cne.21891)
11. Perrotti, L. I. et al. 2005 DeltaFosB accumulates in a GABAergic cell population in the posterior tail of the ventral tegmental area after psychostimulant treatment. Eur. J. Neurosci. 21, 2817-2824. (doi:10.1111/j.1460-9568.2005.04110.x)
12. Lecca, S., Melis, M., Luchicchi, A., Ennas, M. G., Castelli, M. P., Muntoni, A. L. & Pistis, M. 2011 Effects of drugs of abuse on putative rostromedial tegmental neurons, inhibitory afferents tomidbrain dopamine cells. Neuropsychopharmacology 36, 589-602. (doi:10.1038/npp.2010.190)
13. Lecca, S., Melis, M., Luchicchi, A., Muntoni, A. L. & Pistis, M. 2012 Inhibitory inputs from rostromedial tegmental neurons regulate spontaneous activity of midbrain dopamine cells and their responses to drugs of abuse. Neuropsychopharmacology 37, 1164-1176. (doi:10.1038/npp.2011.302)
14. Luscher, C. & Ungless, M. A. 2006 The mechanistic classification of addictive drugs. PLoS Med. 3, e437. (doi:10.1371/journal.pmed.0030437)
15. Jalabert, M., Bourdy, R., Courtin, J., Veinante, P., Manzoni, O. J., Barrot, M. & Georges, F. 2011 Neuronal circuits underlying acute morphine action on dopamine neurons. Proc. Natl Acad. Sci. USA 108, 16446-16450. (doi:10.1073/pnas.1105418108)
16. Matsui, A. & Williams, J. T. 2011 Opioid-sensitive GABA inputs from rostromedial tegmental nucleus synapse onto midbrain dopamine neurons. J. Neurosci. 31, 17729-17735. (doi:10.1523/JNEUROSCI.4570-11.2011)
17. Lobb, C. J., Wilson, C. J. & Paladini, C. A. 2010 A dynamic role for GABA receptors on the firing pattern of midbrain dopaminergic neurons. J. Neurophysiol. 104, 403-413. (doi:10.1152/jn.00204.2010)
18. Morikawa, H. & Paladini, C. A. 2011 Dynamic regulation of midbrain dopamine neuron activity: intrinsic, synaptic, and plasticity mechanisms. Neuroscience 198, 95-111. (doi:10.1016/j.neuroscience.2011.08.023)
19. Marinelli, M., Rudick, C. N., Hu, X. T. & White, F. J. 2006 Excitability of dopamine neurons: modulation and physiological consequences. CNS Neurol. Disord. Drug Targets 5, 79-97. (doi:10.2174/187152706784111542)
20. Grace, A. A. & Onn, S. P. 1989 Morphology and electrophysiological properties of immunocytochemically identified rat dopamine neurons recorded in vitro. J. Neurosci. 9, 3463-3481.
21. Omelchenko, N. & Sesack, S. R. 2009 Ultrastructural analysis of local collaterals of rat ventral tegmental area neurons: GABA phenotype and synapses onto dopamine and GABA cells. Synapse 63, 895-906. (doi:10.1002/syn.20668)
22. Bayer, V. E. & Pickel, V. M. 1991 GABA-labeled terminals form proportionally more synapses with dopaminergic neurons containing low densities of tyrosine hydroxylase-immunoreactivity in rat ventral tegmental area. Brain Res. 559, 44-55. (doi:10.1016/0006-8993(91)90285-4)
23. Sesack, S. R. & Grace, A. A. 2010 Cortico-basal ganglia reward network: microcircuitry. Neuropsychopharmacology 35, 27-47. (doi:10.1038/npp.2009.93)
24. Xia, Y., Driscoll, J. R., Wilbrecht, L., Margolis, E. B., Fields, H. L. & Hjelmstad, G. O. 2011 Nucleus accumbens medium spiny neurons target non-dopaminergic neurons in the ventral tegmental area. J. Neurosci. 31, 7811-7816. (doi:10.1523/JNEUROSCI.1504-11.2011)
25. Jhou, T. C., Fields, H. L., Baxter, M. G., Saper, C. B. & Holland, P. C. 2009 The rostromedial tegmental nucleus (RMTg), a GABAergic afferent to midbrain dopamine neurons, encodes aversive stimuli and inhibits motor responses. Neuron 61, 786-800. (doi:10.1016/j.neuron.2009.02.001)
26. Kaufling, J., Veinante, P., Pawlowski, S. A., Freund-Mercier, M. J. & Barrot, M. 2009 Afferents to the GABAergic tail of the ventral tegmental area in the rat. J. Comp. Neurol. 513, 597-621. (doi:10.1002/cne.21983)
27. Ungless, M. A. 2004 Dopamine: the salient issue. Trends Neurosci. 27, 702-706. (doi:10.1016/j.tins.2004.10.001)
28. Fields, H. L., Hjelmstad, G. O., Margolis, E. B. & Nicola, S. M. 2007 Ventral tegmental area neurons in learned appetitive behavior and positive reinforcement. Annu. Rev. Neurosci. 30, 289-316. (doi:10.1146/annurev.neuro.30.051606.094341)
29. Fernandez-Ruiz, J., Hernandez, M. & Ramos, J. A. 2010 Cannabinoid-dopamine interaction in the pathophysiology and treatment of CNS disorders. CNS Neurosci. Ther. 16, e72-91. (doi:10.1111/j.1755-5949.2010.00144.x)
30. Melis, M., Muntoni, A. L. & Pistis, M. 2012 Endocannabinoids and the processing of value-related signals. Front. Pharmacol. 3, 7. (doi:10.3389/fphar.2012.00007)
31. Marinelli, S. et al. 2007 N-arachidonoyl-dopamine tunes synaptic transmission onto dopaminergic neurons by activating both cannabinoid and vanilloid receptors. Neuropsychopharmacology 32, 298-308. (doi:10.1038/sj.npp.1301118)
32. Kortleven, C., Fasano, C., Thibault, D., Lacaille, J. C. & Trudeau, L. E. 2011 The endocannabinoid 2-arachidonoylglycerol inhibits long-term potentiation of glutamatergic synapses onto ventral tegmental area dopamine neurons in mice. Eur. J. Neurosci. 33, 1751-1760. (doi:10.1111/j.1460-9568.2011.07648.x)
33. Matyas, F., Urban, G. M., Watanabe, M., Mackie, K., Zimmer, A., Freund, T. F. & Katona, I. 2008 Identification of the sites of 2-arachidonoylglycerol synthesis and action imply retrograde endocannabinoid signaling at both GABAergic and glutamatergic synapses in the ventral tegmental area. Neuropharmacology 54, 95-107. (doi:10.1016/j.neuropharm.2007.05.028)
34. Melis, M. et al. 2006 Protective activation of the endocannabinoid system during ischemia in dopamine neurons. Neurobiol. Dis. 24, 15-27. (doi:10.1016/j.nbd.2006.04.010)
35. Kano, M., Ohno-Shosaku, T., Hashimotodani, Y., Uchigashima, M. & Watanabe, M. 2009 Endocannabinoid- mediated control of synaptic transmission. Physiol. Rev. 89, 309-380. (doi:10.1152/physrev.00019.2008)
36. Alger, B. E. 2012 Endocannabinoids at the synapse a decade after the dies mirabilis (29 March 2001): what we still do not know. J. Physiol. 590, 2203-2212. (doi:10.1113/jphysiol.2011.220855)
37. Katona, I. & Freund, T. F. 2012 Multiple functions of endocannabinoid signaling in the brain. Annu. Rev. Neurosci. 35, 529-558. (doi:10.1146/annurev-neuro-062111-150420)
38. Egertova, M., Simon, G. M., Cravatt, B. F. & Elphick, M. R. 2008 Localization of N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) expression in mouse brain: a new perspective on N-acylethanolamines as neural signaling molecules. J. Comp. Neurol. 506, 604-615. (doi:10.1002/cne.21568)
39. Luchicchi, A., Lecca, S., Carta, S., Pillolla, G., Muntoni, A. L., Yasar, S., Goldberg, S. R. & Pistis, M. 2010 Effects of fatty acid amide hydrolase inhibition on neuronal responses to nicotine, cocaine and morphine in the nucleus accumbens shell and ventral tegmental area: involvement of PPAR-alpha nuclear receptors. Addict. Biol. 15, 277-288. (doi:10.1111/j.1369-1600.2010.00222.x)
40. Scherma, M. et al. 2008 Inhibition of anandamide hydrolysis by URB597 reverses abuse-related behavioral and neurochemical effects of nicotine in rats. J. Pharmacol. Exp. Ther. 327, 482-490. (doi:10.1124/jpet.108.142224)
41. Melis, M., Pillolla, G., Luchicchi, A., Muntoni, A. L., Yasar, S., Goldberg, S. R. & Pistis, M. 2008 Endogenous fatty acid ethanolamides suppress nicotine-induced activation of mesolimbic dopamine neurons through nuclear receptors. J. Neurosci. 28, 13985-13994. (doi:10.1523/JNEUROSCI.3221-08.2008)
42. Melis, M., Carta, S., Fattore, L., Tolu, S., Yasar, S., Goldberg, S. R., Fratta, W., Maskos, U. & Pistis, M. 2010 Peroxisome proliferator-activated receptors-alpha modulate dopamine cell activity through nicotinic receptors. Biol. Psychiatry 68, 256-264. (doi:10.1016/j.biopsych.2010.04.016)
43. Mascia, P. et al. 2011 Blockade of nicotine reward and reinstatement by activation of alpha-type peroxisome proliferator-activated receptors. Biol. Psychiatry 69, 633-641. (doi:10.1016/j.biopsych.2010.07.009)
44. Matsumoto, M. & Hikosaka, O. 2009 Two types of dopamine neuron distinctly convey positive and negative motivational signals. Nature 459, 837-841. (doi:10.1038/nature08028)
45. Bromberg-Martin, E. S. & Hikosaka, O. 2009 Midbrain dopamine neurons signal preference for advance information about upcoming rewards. Neuron 63, 119-126. (doi:10.1016/j.neuron.2009.06.009)
46. Grace, A. A., Floresco, S. B., Goto, Y. & Lodge, D. J. 2007 Regulation of firing of dopaminergic neurons and control of goal-directed behaviors. Trends Neurosci. 30, 220-227. (doi:10.1016/j.tins.2007.03.003)
47. Valenti, O. & Grace, A. A. 2010 Antipsychotic druginduced increases in ventral tegmental area dopamine neuron population activity via activation of the nucleus accumbens-ventral pallidum pathway. Int. J. Neuropsychopharmacol. 13, 845-860. (doi:10.1017/S1461145709990599)
48. Pan, B., Hillard, C. J. & Liu, Q. S. 2008 Endocannabinoid signaling mediates cocaine-induced inhibitory synaptic plasticity in midbrain dopamine neurons. J. Neurosci. 28, 1385-1397. (doi:10.1523/JNEUROSCI.4033-07.2008)
49. Riegel, A. C. & Lupica, C. R. 2005 Independent presynaptic and postsynaptic mechanisms regulate endocannabinoid signaling at multiple synapses in the ventral tegmental area. J. Neurosci. 24, 11070-11078. (doi:10.1523/JNEUROSCI.3695-04.2004)
50. Melis, M., Perra, S., Muntoni, A. L., Pillolla, G., Lutz, B., Marsicano, G., Di Marzo, V., Gessa, G. L. & Pistis, M. 2004 Prefrontal cortex stimulation induces 2-arachidonoyl- glycerol-mediated suppression of excitation in dopamine neurons. J. Neurosci. 24, 10707-10715. (doi:10.1523/JNEUROSCI.3502-04.2004)
51. Szabo, B., Siemes, S. & Wallmichrath, I. 2002 Inhibition of GABAergic neurotransmission in the ventral tegmental area by cannabinoids. Eur. J. Neurosci. 15, 2057-2061. (doi:10.1046/j.1460-9568.2002.02041.x)
52. Melis, M., Pistis, M., Perra, S., Muntoni, A. L., Pillolla, G. & Gessa, G. L. 2004 Endocannabinoids mediate presynaptic inhibition of glutamatergic transmission in rat ventral tegmental area dopamine neurons through activation of CB1 receptors. J. Neurosci. 24, 53-62. (doi:10.1523/JNEUROSCI.4503-03.2004)
53. Haj-Dahmane, S. & Shen, R. Y. 2010 Regulation of plasticity of glutamate synapses by endocannabinoids and the cyclic-AMP/protein kinase A pathway in midbrain dopamine neurons. J. Physiol. 588, 2589-2604. (doi:10.1113/jphysiol.2010.190066)
54. Marinelli, S., Di Marzo, V., Berretta, N., Matias, I., Maccarrone, M., Bernardi, G. & Mercuri, N. B. 2003 Presynaptic facilitation of glutamatergic synapses to dopaminergic neurons of the rat substantia nigra by endogenous stimulation of vanilloid receptors. J. Neurosci. 23, 3136-3144.
55. Geisler, S., Derst, C., Veh, R. W. & Zahm, D. S. 2007 Glutamatergic afferents of the ventral tegmental area in the rat. J. Neurosci. 27, 5730-5743. (doi:10.1523/JNEUROSCI.0012-07.2007)
56. Chen, B. T., Bowers, M. S., Martin, M., Hopf, F. W., Guillory, A. M., Carelli, R. M., Chou, J. K. & Bonci, A. 2008 Cocaine but not natural reward self-administration nor passive cocaine infusion produces persistent LTP in the VTA. Neuron 59, 288-297. (doi:10.1016/j.neuron.2008.05.024)
57. Gessa, G. L., Melis, M., Muntoni, A. L. & Diana, M. 1998 Cannabinoids activate mesolimbic dopamine neurons by an action on cannabinoid CB1 receptors. Eur. J. Pharmacol. 341, 39-44. (doi:10.1016/S0014-2999(97)01442-8)
58. French, E. D. 1997 Delta9-tetrahydrocannabinol excites rat VTA dopamine neurons through activation of cannabinoid CB1 but not opioid receptors. Neurosci. Lett. 226, 159-162. (doi:10.1016/S0304-3940(97)00278-4)
59. Lodge, D. J. & Grace, A. A. 2006 The laterodorsal tegmentum is essential for burst firing of ventral tegmental area dopamine neurons. Proc. Natl Acad. Sci. USA 103, 5167-5172. (doi:10.1073/pnas.0510715103)
60. Schilstrom, B., Rawal, N., Mameli-Engvall, M., Nomikos, G. G. & Svensson, T. H. 2003 Dual effects of nicotine on dopamine neurons mediated by different nicotinic receptor subtypes. Int. J. Neuropsychopharmacol. 6, 1-11. (doi:10.1017/S1461145702003188)
61. Mameli-Engvall, M., Evrard, A., Pons, S., Maskos, U., Svensson, T. H., Changeux, J. P. & Faure, P. 2006 Hierarchical control of dopamine neuron-firing patterns by nicotinic receptors. Neuron 50, 911-921. (doi:10.1016/j.neuron.2006.05.007)
62. Clarke, P. B., Schwartz, R. D., Paul, S.M., Pert, C. B. & Pert, A. 1985 Nicotinic binding in rat brain: autoradiographic comparison of [3H]acetylcholine, [3H]- nicotine, and [125I]-alpha-bungarotoxin. J. Neurosci. 5, 1307-1315.
63. Pistis, M. & Melis, M. 2010 From surface to nuclear receptors: the endocannabinoid family extends its assets. Curr. Med. Chem. 17, 1450-1467. (doi:10.2174/092986710790980014)
64. Ueda, N., Puffenbarger, R. A., Yamamoto, S. & Deutsch, D. G. 2000 The fatty acid amide hydrolase (FAAH). Chem. Phys. Lipids 108, 107-121. (doi:10.1016/S0009-3084(00)00190-0)
65. Tsuboi, K. et al. 2011 Enzymatic formation of N-acylethanolamines from N-acylethanolamine plasmalogen through N-acylphosphatidylethanolamine-hydrolyzing phospholipase D-dependent and -independent pathways. Biochim. Biophys. Acta 1811, 565-577. (doi:10.1016/j.bbalip.2011.07.009)
66. Fu, J. et al. 2003 Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha. Nature 425, 90-93. (doi:10.1038/nature01921)
67. Lo Verme, J., Fu, J., Astarita, G., La Rana, G., Russo, R., Calignano, A. & Piomelli, D. 2005 The nuclear receptor peroxisome proliferator-activated receptoralpha mediates the anti-inflammatory actions of palmitoylethanolamide. Mol. Pharmacol. 67, 15-19. (doi:10.1124/mol.104.006353)
68. Lambert, D. M. & Di Marzo, V. 1999 The palmitoylethanolamide and oleamide enigmas: are these two fatty acid amides cannabimimetic? Curr. Med. Chem. 6, 757-773.
69. Smart, D., Jonsson, K. O., Vandevoorde, S., Lambert, D. M. & Fowler, C. J. 2002 'Entourage' effects of Nacyl ethanolamines at human vanilloid receptors. Comparison of effects upon anandamide-induced vanilloid receptor activation and upon anandamide metabolism. Br. J. Pharmacol. 136, 452-458. (doi:10.1038/sj.bjp.0704732)
70. Di Marzo, V., Melck, D., Orlando, P., Bisogno, T., Zagoory, O., Bifulco, M., Vogel, Z. & De Petrocellis, L. 2001 Palmitoylethanolamide inhibits the expression of fatty acid amide hydrolase and enhances the antiproliferative effect of anandamide in human breast cancer cells. Biochem. J. 358, 249-255. (doi:10.1042/0264-6021:3580249)
71. De Petrocellis, L., Davis, J. B. & Di Marzo, V. 2001 Palmitoylethanolamide enhances anandamide stimulation of human vanilloid VR1 receptors. FEBS Lett. 506, 253-256. (doi:10.1016/S0014-5793(01)02934-9)
72. Jonsson, K. O., Vandevoorde, S., Lambert, D. M., Tiger, G. & Fowler, C. J. 2001 Effects of homologues and analogues of palmitoylethanolamide upon the inactivation of the endocannabinoid anandamide. Br. J. Pharmacol. 133, 1263-1275. (doi:10.1038/sj.bjp.0704199)
73. Panlilio, L. V. et al. 2012 Novel use of a lipid-lowering fibrate medication to prevent nicotine reward and relapse: preclinical findings. Neuropsychopharmacology 37, 1838-1847. (doi:10.1038/npp.2012.31)
74. Hansen, H. H., Ikonomidou, C., Bittigau, P., Hansen, S. H. & Hansen, H. S. 2001 Accumulation of the anandamide precursor and other N-acylethanolamine phospholipids in infant rat models of in vivo necrotic and apoptotic neuronal death. J. Neurochem. 76, 39-46. (doi:10.1046/j.1471-4159.2001.00006.x)
75. Stella, N. & Piomelli, D. 2001 Receptor-dependent formation of endogenous cannabinoids in cortical neurons. Eur. J. Pharmacol. 425, 189-196. (doi:10.1016/S0014-2999(01)01182-7)
76. Cheer, J. F., Wassum, K. M., Heien, M. L., Phillips, P. E. & Wightman, R. M. 2004 Cannabinoids enhance subsecond dopamine release in the nucleus accumbens of awake rats. J. Neurosci. 24, 4393-4400. (doi:10.1523/JNEUROSCI.0529-04.2004)
77. Giuffrida, A. & Seillier, A. 2012 New insights on endocannabinoid transmission in psychomotor disorders. Prog. Neuropsychopharmacol. Biol. Psychiatry 38, 51-58. (doi:10.1016/j.pnpbp.2012.04.002)
78. Oleson, E. B. et al. 2012 Endocannabinoids shape accumbal encoding of cue-motivated behavior via CB1 receptor activation in the ventral tegmentum. Neuron 73, 360-373. (doi:10.1016/j.neuron.2011.11.018)
79. Cheer, J. F., Heien, M. L., Garris, P. A., Carelli, R.M. & Wightman, R. M. 2005 Simultaneous dopamine and single-unit recordings reveal accumbens GABAergic responses: implications for intracranial self-stimulation. Proc. Natl Acad. Sci. USA 102, 19150-19155. (doi:10.1073/pnas.0509607102)
80. Olds, J. & Milner, P. 1954 Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain. J. Comp. Physiol. Psychol. 47, 419-427. (doi:10.1037/h0058775)
81. Witten, I. B. et al. 2011 Recombinase-driver rat lines: tools, techniques, and optogenetic application to dopamine- mediated reinforcement. Neuron 72, 721-733. (doi:10.1016/j.neuron.2011.10.028)
82. Deroche-Gamonet, V., Le Moal, M., Piazza, P. V. & Soubrie, P. 2001 SR141716, a CB1 receptor antagonist, decreases the sensitivity to the reinforcing effects of electrical brain stimulation in rats. Psychopharmacology 157, 254-259. (doi:10.1007/s002130100804)
83. Pillolla, G., Melis, M., Perra, S., Muntoni, A. L., Gessa, G. L. & Pistis, M. 2007 Medial forebrain bundle stimulation evokes endocannabinoid-mediated modulation of ventral tegmental area dopamine neuron firing in vivo. Psychopharmacology 191, 843-853. (doi:10.1007/s00213-007-0733-z)
84. Kuhr, W. G., Wightman, R. M. & Rebec, G. V. 1987 Dopaminergic neurons: simultaneous measurements of dopamine release and single-unit activity during stimulation of the medial forebrain bundle. Brain Res. 418, 122-128. (doi:10.1016/0006-8993(87)90968-1)
85. Fibiger, H. C., LePiane, F. G., Jakubovic, A. & Phillips, A. G. 1987 The role of dopamine in intracranial selfstimulation of the ventral tegmental area. J. Neurosci. 7, 3888-3896.
86. Kenny, P. J. & Markou, A. 2005 Conditioned nicotine withdrawal profoundly decreases the activity of brain reward systems. J. Neurosci. 25, 6208-6212. (doi:10.1523/JNEUROSCI.4785-04.2005)
87. Kenny, P. J., Chen, S. A., Kitamura, O., Markou, A. & Koob, G. F. 2006 Conditioned withdrawal drives heroin consumption and decreases reward sensitivity. J. Neurosci. 26, 5894-5900. (doi:10.1523/JNEUROSCI.0740-06.2006)
88. American Psychiatric Association. 2000 Diagnostic and statistical manual of mental disorders, 4th edn. DSM-IVTR. Washington, DC: American Psychiatric Association.
89. Schultz, W., Dayan, P. & Montague, P. R. 1997 A neural substrate of prediction and reward. Science 275, 1593-1599. (doi:10.1126/science.275.5306.1593)
90. van Zessen, R., Phillips, J. L., Budygin, E. A. & Stuber, G. D. 2012 Activation of VTA GABA neurons disrupts reward consumption. Neuron 73, 1184-1194. (doi:10.1016/j.neuron.2012.02.016)
91. Serrano, A. & Parsons, L. H. 2011 Endocannabinoid influence in drug reinforcement, dependence and addiction-related behaviors. Pharmacol. Ther. 132, 215-241. (doi:10.1016/j.pharmthera.2011.06.005)
92. Vaughn, L. K., Mantsch, J. R., Vranjkovic, O., Stroh, G., Lacourt, M., Kreutter, M. & Hillard, C. J. 2012 Cannabinoid receptor involvement in stress-induced cocaine reinstatement: potential interaction with noradrenergic pathways. Neuroscience 204, 117-124. (doi:10.1016/j.neuroscience.2011.08.021)
93. Christensen, R., Kristensen, P. K., Bartels, E. M., Bliddal, H. & Astrup, A. 2007 Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials. Lancet 370, 1706-1713. (doi:10.1016/S0140-6736(07)61721-8)
94. Horder, J., Harmer, C. J., Cowen, P. J. & McCabe, C. 2010 Reduced neural response to reward following 7 days treatment with the cannabinoid CB1 antagonist rimonabant in healthy volunteers. Int. J. Neuropsychopharmacol. 13, 1103-1113. (doi:10.1017/S1461145710000453)
95. Navarro, M. et al. 2001 Functional interaction between opioid and cannabinoid receptors in drug self-administration. J. Neurosci. 21, 5344-5350.
96. De Vries, T. J., Shaham, Y., Homberg, J. R., Crombag, H., Schuurman, K., Dieben, J., Vanderschuren, L. J. & Schoffelmeer, A. N. 2001 A cannabinoid mechanism in relapse to cocaine seeking. Nat. Med. 7, 1151-1154. (doi:10.1038/nm1001-1151)
97. Cohen, C., Perrault, G., Voltz, C., Steinberg, R. & Soubrie, P. 2002 SR141716, a central cannabinoid (CB(1)) receptor antagonist, blocks the motivational and dopamine-releasing effects of nicotine in rats. Behav. Pharmacol. 13, 451-463. (doi:10.1097/00008877-200209000-00018)
98. Rigotti, N. A., Gonzales, D., Dale, L. C., Lawrence, D. & Chang, Y. 2009 A randomized controlled trial of adding the nicotine patch to rimonabant for smoking cessation: efficacy, safety and weight gain. Addiction 104, 266-276. (doi:10.1111/j.1360-0443.2008.02454.x)
99. Colombo, G., Agabio, R., Fa, M., Guano, L., Lobina, C., Loche, A., Reali, R. & Gessa, G. L. 1998 Reduction of voluntary ethanol intake in ethanol-preferring sP rats by the cannabinoid antagonist SR-141716. Alcohol Alcohol. 33, 126-130. (doi:10.1093/oxfordjournals.alcalc.a008368)
100. Spano, M. S., Fattore, L., Cossu, G., Deiana, S., Fadda, P. & Fratta, W. 2004 CB1 receptor agonist and heroin, but not cocaine, reinstate cannabinoidseeking behaviour in the rat. Br. J. Pharmacol. 143, 343-350. (doi:10.1038/sj.bjp.0705932)
101. Justinova, Z., Munzar, P., Panlilio, L. V., Yasar, S., Redhi, G. H., Tanda, G. & Goldberg, S. R. 2008 Blockade of THC-seeking behavior and relapse in monkeys by the cannabinoid CB(1)-receptor antagonist rimonabant. Neuropsychopharmacology 33, 2870-2877. (doi:10.1038/npp.2008.21)
102. Fattore, L., Deiana, S., Spano, S. M., Cossu, G., Fadda, P., Scherma, M. & Fratta, W. 2005 Endocannabinoid system and opioid addiction: behavioural aspects. Pharmacol. Biochem. Behav. 81, 343-359. (doi:10.1016/j.pbb.2005.01.031)
103. Fattore, L., Spano, M. S., Cossu, G., Deiana, S. & Fratta, W. 2003 Cannabinoid mechanism in reinstatement of heroin-seeking after a long period of abstinence in rats. Eur. J. Neurosci. 17, 1723-1726. (doi:10.1046/j.1460-9568.2003.02607.x)
104. Lopez-Moreno, J. A., Gonzalez-Cuevas, G., de Fonseca, F. R. & Navarro, M. 2004 Long-lasting increase of alcohol relapse by the cannabinoid receptor agonist WIN 55,212-2 during alcohol deprivation. J. Neurosci. 24, 8245-8252. (doi:10.1523/JNEUROSCI.2179-04.2004)
105. McGregor, I. S., Dam, K. D., Mallet, P. E. & Gallate, J. E. 2005 D9-THC reinstates beer- and sucrose-seeking behaviour in abstinent rats: comparison with midazolam, food deprivation and predator odour. Alcohol Alcohol. 40, 35-45. (doi:10.1093/alcalc/agh113)
106. Gamaleddin, I., Wertheim, C., Zhu, A. Z., Coen, K. M., Vemuri, K., Makryannis, A., Goldberg, S. R. & Le Foll, B. 2012 Cannabinoid receptor stimulation increases motivation for nicotine and nicotine seeking. Addict. Biol. 17, 47-61. (doi:10.1111/j.1369-1600.2011.00314.x)
107. Scherma, M. et al. 2012 The anandamide transport inhibitor AM404 reduces the rewarding effects of nicotine and nicotine-induced dopamine elevations in the nucleus accumbens shell in rats. Br. J. Pharmacol. 165, 2539-2548. (doi:10.1111/j.1476-5381.2011.01467.x)
108. Gamaleddin, I., Guranda, M., Goldberg, S. R. & Le Foll, B. 2011 The selective anandamide transport inhibitor VDM11 attenuates reinstatement of nicotine seeking behaviour, but does not affect nicotine intake. Br. J. Pharmacol. 164, 1652-1660. (doi:10.1111/j.1476-5381.2011.01440.x)
109. Justinova, Z. et al. 2008 Fatty acid amide hydrolase inhibition heightens anandamide signaling without producing reinforcing effects in primates. Biol. Psychiatry 64, 930-937. (doi:10.1016/j.biopsych.2008.08.008)
110. Bortolato, M. et al. 2006 Anxiolytic-like properties of the anandamide transport inhibitor AM404. Neuropsychopharmacology 31, 2652-2659. (doi:10.1038/sj.npp.1301061)
111. Forget, B., Coen, K. M. & Le Foll, B. 2009 Inhibition of fatty acid amide hydrolase reduces reinstatement of nicotine seeking but not break point for nicotine self-administration-comparison with CB(1) receptor blockade. Psychopharmacology 205, 613-624. (doi:10.1007/s00213-009-1569-5)
112. Scherma, M. et al. 2008 The endogenous cannabinoid anandamide has effects on motivation and anxiety that are revealed by fatty acid amide hydrolase (FAAH) inhibition. Neuropharmacology 54, 129-140. (doi:10.1016/j.neuropharm.2007.08.011)
113. Parker, S. L., Fu, Y., McAllen, K., Luo, J., McIntosh, J. M., Lindstrom, J. M. & Sharp, B. M. 2004 Up-regulation of brain nicotinic acetylcholine receptors in the rat during long-term self-administration of nicotine: disproportionate increase of the alpha6 subunit. Mol. Pharmacol. 65, 611-622. (doi:10.1124/mol.65.3.611)
114. Mugnaini, M., Tessari, M., Tarter, G., Merlo Pich, E., Chiamulera, C. & Bunnemann, B. 2002 Upregulation of [3H]methyllycaconitine binding sites following continuous infusion of nicotine, without changes of alpha7 or alpha6 subunit mRNA: an autoradiography and in situ hybridization study in rat brain. Eur. J. Neurosci. 16, 1633-1646. (doi:10.1046/j.1460-9568.2002.02220.x)
115. Nashmi, R. et al. 2007 Chronic nicotine cell specifically upregulates functional alpha 4* nicotinic receptors: basis for both tolerance in midbrain and enhanced long-term potentiation in perforant path. J. Neurosci. 27, 8202-8218. (doi:10.1523/JNEUROSCI.2199-07.2007)
116. Jackevicius, C. A., Tu, J. V., Ross, J. S., Ko, D. T., Carreon, D. & Krumholz, H. M. 2011 Use of fibrates in the United States and Canada. J. Am. Med. Assoc. 305, 1217-1224. (doi:10.1001/jama.2011.353)