title: The role of the CB1 cannabinoid receptor and its endogenous ligands, anandamide and 2-arachidonoylglycerol, in amphetamine-induced behavioural sensitization.
abstract: Cannabinoid receptors and their endogenous ligands (endocannabinoids) have been implicated in cocaine and amphetamine reward. Their role in psychostimulant-induced behavioural sensitization still has to be determined. The purpose of the present study was, for one, to compare the effects of a pharmacological and genetic manipulation of CB(1) cannabinoid receptors on amphetamine-induced locomotor sensitization in mice, and, secondly, to quantify the concentration of anandamide and 2-arachidonoylglycerol in different forebrain areas of behaviourally sensitized animals. The results can be summarized as follows: CB(1) knockout mice failed to sensitize to the locomotor stimulant effects of amphetamine. On the contrary, administration of the CB(1) receptor antagonist SR141716A (rimonabant; 3mg/kg; i.p.) increased amphetamine sensitization in wild-type animals, indicating that the difference between CB(1) knockouts and SR141716A treated animals could be due to the 'chronic' versus 'acute' loss of CB(1) receptor function, or, alternatively, that SR141716A could exert pharmacological effects beyond its proposed CB(1) antagonistic action. Furthermore, sensitized wild-type mice and animals, which had received a single amphetamine injection on the challenge day, both had increased anandamide concentrations in the dorsal striatum and decreased anandamide levels in the ventral striatum, comprising nucleus accumbens. 2-Arachidonoylglycerol levels were decreased in the ventral striatum of sensitized animals only. Together, these findings suggest that prolonged activation of dopamine receptors could alter endocannabinoid levels and support the proposed involvement of the CB(1) receptor in amphetamine sensitization.
authors.affiliation: School of Psychology, Neuroscience Research Unit, University of Hertfordshire, College Lane, Hatfield, Herts AL10 9AB, UK.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Thiemann
authors.forename: Mario
authors.initials: M
authors.lastname: van der Stelt
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrosino
authors.forename: Areles
authors.initials: A
authors.lastname: Molleman
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.forename: Rüdiger U
authors.initials: RU
authors.lastname: Hasenöhrl
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D063388:Endocannabinoids; D005989:Glycerides / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism; D018709:Statistics, Nonparametric
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D000697:Central Nervous System Stimulants; D063388:Endocannabinoids; D005989:Glycerides; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D011954:Receptors, Dopamine; C094503:glyceryl 2-arachidonate; D000661:Amphetamine; C078814:anandamide