Review article Interactions between the cannabinoid and dopaminergic systems: Evidence from animal studies Marie-Anne El Khoury a, b, c , Victor Gorgievski a, b, c , Larissa Moutsimilli a, b, c , Bruno Giros a, b, c, d , Eleni T. Tzavara a, b, c, ⁎ a Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS-952, Université Pierre et Marie Curie, 9 quai St Bernard, 75005 Paris, France b UPMC, Université Paris 06, Pathophysiology of CNS Disorders, 9 quai St Bernard, 75005 Paris, France c Centre National de la Recherche Scientifique (CNRS) UMR7224, Université Pierre et Marie Curie, 9 quai St Bernard, 75005 Paris, France d Douglas Hospital Research Center, Dpt of Psychiatry McGill University, Montreal, Canada abstract article info Article history: Received 16 October 2011 Received in revised form 18 December 2011 Accepted 18 December 2011 Available online 20 January 2012 Keywords: Attentional set shifting Cognition Dopamine transporter knock out mice Metabotropic glutamate receptors Psychosis TRPV1 There is a prominent role of the cannabinoid system to control basal ganglia function, in respect to reward, psychomotor function and motor control. Cannabinoid dysregulations might have a pathogenetic role in dopamine- and basal ganglia related neuropsychiatric disorders, such as drug addiction, psychosis, Parkin- son's disease and Huntington's disease. This review highlights interactions between cannabinoids, and dopa- mine, to modulate neurotransmitter release and synaptic plasticity in the context of drug addiction, psychosis and cognition. Modulating endocannabinoid function, as a plasticity based therapeutic strategy, in the above pathologies with particular focus on cannabinoid receptor type 1 (CB1 receptor) antagonists/inverse ago- nists, is discussed. On the basis of the existing literature and of new experimental evidence presented here, CB1 receptor antagonists might be beneficial in disease states associated with hedonic dysregulation, and with cognitive dysfunction in particular in the context of psychosis. It is suggested that this effects might be mediated via a hyperglutamatergic state through metabotropic glutamate activation. Indications for endo- cannabinoid catabolism inhibitors in psychiatric disorders, that might be CB1 receptor independent and might involve TRPV1 receptors, are also discussed. © 2012 Elsevier Inc. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 2. Cannabinoid–dopamine interactions: evidence from anatomical studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 2.1. General considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 2.2. Cannabinoid receptor expression in dopaminergic regions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 3. Dopamine and cannabinoid interactions: functional inter-regulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 3.1. Cannabinoids increase DA neuronal firing and synaptic DA release in the striatum . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 3.2. Dopamine modulates cannabinoid release in the striatum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 3.3. Cannabinoids modulate DA release in the prefrontal cortex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 3.4. Cannabinoids regulate ACh efflux, in a DA dependent manner . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 4. Dopamine, cannabinoid and glutamate interactions: regulation of synaptic plasticity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 4.1. Plastic interactions between DA and glutamate in the mesocorticolimbic projection and their regulation by endocannabinoids . . . . . . 40 4.2. Modulation of synaptic plasticity by endocannabinoids: regulation by metabotropic receptors. . . . . . . . . . . . . . . . . . . . . . 42 5. Dopamine and cannabinoid interactions: behavioral studies and therapeutic potential of CB1 receptor antagonists . . . . . . . . . . . . . . . 43 5.1. Cannabinoids and dopamine in drug addiction; antiaddictive effects of CB1 receptor antagonists . . . . . . . . . . . . . . . . . . . . 43 Progress in Neuro-Psychopharmacology & Biological Psychiatry 38 (2012) 36–50 Abbreviations: 2AG, 2Arachidonoylglycerol; AA5HT, N-[2-(5-Hydroxy-1H-indol-3-yl)ethyl]-5,8,11,14-eicosatetraenamide; AM404, 5,8,11,14-eicosatetraenamide, N-(4-hydroxyphenyl)- (5Z,8Z,11Z,14Z) (9CI); AM251, N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; Anandamide, N-arachidonoylethanolamide- 5,8,11,14-eicosatetraenamide, N-(2-hydroxyethyl)-(5Z,8Z,11Z,14Z)-(9CI); NADA, N-Arachidonyldopamine; SR141716A, rimonabant 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4- methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide; THC, delta-9-tetrahydrocannabinol; URB597, (3′-(aminocarbonyl)[1,1′-biphenyl]-3-yl)-cyclohexylcarbamate; VDM11, N-arachidonoyl-(2-methyl-4-hydroxyphenyl) amine; WIN55,212-3, [(3S)-2,3-Dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenyl- methanone monomethanesulfonate. ⁎ Corresponding author at: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS-952, Université Pierre et Marie Curie, 9 quai St Bernard, 75005 Paris, France. E-mail address: eleni.tzavara@snv.jussieu.fr (E.T. Tzavara). 0278-5846/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2011.12.005 Contents lists available at SciVerse ScienceDirect Progress in Neuro-Psychopharmacology & Biological Psychiatry journal homepage: www.elsevier.com/locate/pnp