title: On the role of A₂A and D₂ receptors in control of cocaine and food-seeking behaviors in rats.
abstract: Recent studies indicate that adenosine may influence dopamine neurotransmission via A2A receptors which antagonistically interact with D2 receptor-mediated signaling in the brain. We examined the effects of selective A2A receptor ligands such as the agonist CGS 21680 and the antagonists KW 6002 or SCH 58261 as well as of the D2-like receptor antagonist raclopride on reinstatement of cocaine seeking induced by cocaine, the cocaine-conditioned cue, or the D2-like receptor agonist quinpirole in rats. For comparison, effects of the A2A receptor ligands on reinstatement of food seeking were also studied. CGS 21680 significantly attenuated the reinstatement of cocaine (ip) seeking, and even more potently it reduced quinpirole (ip) or the cue-induced relapse of cocaine seeking as well as cue-induced food seeking. A potent reduction toward the cocaine-, quinpirole-, or cue-induced reinstatement of cocaine seeking was seen with raclopride. Pretreatment with KW 6002 or SCH 58261 reinstated cocaine seeking, and such increases were blocked by raclopride. In the higher doses, KW 6002 or SCH 58261 evoked food-seeking. In combination with the subthreshold dose of cocaine (2.5 mg/kg) or with the cue, low doses of KW 6002 but not SCH 58261 reinstated cocaine-seeking behavior, while none of the A2A receptor antagonists affected the cue-induced food-seeking behavior. The results indicate that A2A activation and D2-like receptor blockade counteract cocaine and food relapse. It is proposed that A2A receptor- and D2 receptor-mediated adenosine and dopamine signaling antagonistically interact in the striato-pallidal GABA neurons to regulate cocaine and food-seeking behavior.
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Kraków, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Wydra
authors.forename: Agata
authors.initials: A
authors.lastname: Suder
authors.forename: Dasiel O
authors.initials: DO
authors.lastname: Borroto-Escuela
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Filip
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy / Q000523:psychology*; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects / Q000523:psychology*; D008297:Male; D019257:Quinpirole / Q000494:pharmacology; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D012646:Self Administration
chemical_list: C547770:Adra2a protein, rat; D018341:Receptors, Adrenergic, alpha-2; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D020891:Raclopride; D003042:Cocaine