title: Effect of the cannabinoid CB1 receptor antagonist SR-141716A on ethanol self-administration and ethanol-seeking behaviour in rats.
abstract: BACKGROUND
  It has been suggested that endocannabinoid mechanisms are involved in the control of ethanol consumption.
  
  
  OBJECTIVE
  The aims of the present study were (1) to evaluate the role of the endocannabinoid system in the control of operant ethanol self-administration and in the reinstatement of ethanol seeking, when induced by stress or conditioned stimuli and (2) to offer new insights on the specificity of such a role.
  
  
  METHODS
  Rats were administered intraperitoneally with the selective cannabinoid CB1 receptor antagonist, SR-141716A, 30 min before operant self-administration or reinstatement sessions. Two schedules of reinforcement, the fixed-ratio 1 (FR1) and the progressive ratio (PR), were used to study 10% (w/v) alcohol and 5.0% sucrose self-administration. NaCl (2% w/v) intake in sodium-depleted rats was studied only under the FR1 program.
  
  
  RESULTS
  Treatment with SR-141716A (0.3-3.0 mg/kg) significantly attenuated FR1 alcohol self-administration and lowered the break point for ethanol under PR. SR-141716A also markedly inhibited the reinstatement of alcohol seeking elicited by presentation of cues predictive of drug availability. Conversely, the cannabinoid antagonist did not prevent the reinstatement of alcohol seeking induced by foot-shock stress. Lever pressing for sucrose under FR1 and PR schedules was also significantly decreased by SR-141716A treatment, whereas the drug modestly and only at the highest dose decreased 2% NaCl self-administration.
  
  
  CONCLUSIONS
  Results emphasize that endocannabinoid mechanisms play a major role in the control of ethanol self-administration and in the reinstatement of conditioned ethanol seeking. However, these effects extend to the control of operant behaviours motivated by natural rewards (i.e. sucrose). On the other hand, SR-141716A only weakly reduces NaCl self-administration in sodium-depleted rats, in which salt intake is largely controlled by homeostatic mechanisms. Overall, these observations demonstrate that the inhibition of operant behaviour following blockade of CB1 receptors by SR-141716A is linked to a reduction of reward-related responding and is not related to drug-induced motor deficits.
authors.affiliation: Department of Experimental Medicine and Public Health, University of Camerino, Via Scalzino 3, 62032, Camerino, Italy.
authors.forename: Daina
authors.initials: D
authors.lastname: Economidou
authors.forename: Laura
authors.initials: L
authors.lastname: Mattioli
authors.forename: Carlo
authors.initials: C
authors.lastname: Cifani
authors.forename: Marina
authors.initials: M
authors.lastname: Perfumi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Massi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cuomo
authors.forename: Luigia
authors.initials: L
authors.lastname: Trabace
authors.forename: Roberto
authors.initials: R
authors.lastname: Ciccocioppo
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy* / Q000523:psychology; D000818:Animals; D002492:Central Nervous System Depressants / Q000097:blood; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D004597:Electroshock; D000431:Ethanol / Q000097:blood; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D012055:Reinforcement Schedule; D000077285:Rimonabant; D012646:Self Administration; D012965:Sodium Chloride / Q000494:pharmacology; D013395:Sucrose / Q000494:pharmacology
chemical_list: D002492:Central Nervous System Depressants; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000431:Ethanol; D012965:Sodium Chloride; D013395:Sucrose; D000077285:Rimonabant