title: The adenosine A2A receptor agonist CGS 21680 decreases ethanol self-administration in both non-dependent and dependent animals.
abstract: There is emerging evidence that the adenosinergic system might be involved in drug addiction and alcohol dependence. We have already demonstrated the involvement of A2A receptors (A2AR) in ethanol-related behaviours in mice. Here, we investigated whether the A2AR agonist CGS 21680 can reduce ethanol operant self-administration in both non-dependent and ethanol-dependent Wistar rats. To rule out a potential involvement of the A1R in the effects of CGS 21680, we also tested its effectiveness to reduce ethanol operant self-administration in both heterozygous and homozygous A1R knockout mice. Our results demonstrated that CGS 21680 (0.065, 0.095 and 0.125 mg/kg, i.p.) had a bimodal effect on 10% ethanol operant self-administration in non-dependent rats. The intermediate dose was also effective in reducing 2% sucrose self-administration. Interestingly, the intermediate dose reduced 10% ethanol self-administration in dependent animals more effectively (75% decrease) when compared with non-dependent animals (57% decrease). These results suggest that the A2AR are involved in CGS 21680 effects since the reduction of ethanol self-administration was not dependent upon the presence of A1R in mice. In conclusion, our findings demonstrated the effectiveness of the A2AR agonist CGS 21680 in a preclinical model of alcohol addiction and suggested that the adenosinergic pathway is a promising target to treat alcohol addiction.
authors.affiliation: Groupe de Recherche sur l'Alcool & les Pharmacodépendances, INSERM ERi, UFR de Pharmacie, Université de Picardie Jules Verne, France. hakim.houchi@u-picardie.fr
authors.forename: Hakim
authors.initials: H
authors.lastname: Houchi
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Persyn
authors.forename: Rémi
authors.initials: R
authors.lastname: Legastelois
authors.forename: Mickaël
authors.initials: M
authors.lastname: Naassila
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000437:Alcoholism / Q000188:drug therapy* / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D000431:Ethanol / Q000008:administration & dosage*; D005518:Food Preferences / Q000187:drug effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009042:Motivation / Q000187:drug effects; D010627:Phenethylamines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000235:genetics / Q000502:physiology; D043683:Receptors, Adenosine A2 / Q000502:physiology; D012055:Reinforcement Schedule; D012201:Reward; D012646:Self Administration; D013395:Sucrose / Q000008:administration & dosage
chemical_list: D058908:Adenosine A2 Receptor Agonists; D010627:Phenethylamines; D043682:Receptor, Adenosine A1; D043683:Receptors, Adenosine A2; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000431:Ethanol; D013395:Sucrose; D000241:Adenosine
keywords: A2A receptor; adenosine; agonist; alcohol dependence; knockout; reward