title: Dopamine D3 as well as D2 receptor ligands attenuate the cue-induced cocaine-seeking in a relapse model in rats.
abstract: Environmental cues associated with the previously abused drug elicit craving and relapse to drug use in humans. Several reinstatement paradigms are used in animals to examine the relapse-preventing efficacy of possible medical treatments. The purpose of the present study was to investigate the effect of D3 dopamine receptor ligands in a relapse model where animals with stable cocaine self-administration behavior were exposed to all the environmental and reinforcement-contingent discrete cues associated for the previous cocaine-intake in a single extinction session after 3-week long abstinence period. The following compounds were studied: SB-277011-A as a selective D3 antagonist, BP-897 as a D3 partial agonist/D2 antagonist and haloperidol as a preferential D2 receptor antagonist. In addition, in the same paradigm we investigated the effect of the above ligands on relapse to natural reward-seeking behavior using sucrose as natural reward. SB-277011-A (5 and 20 mg/kg), BP-897 (1 mg/kg) and haloperidol (0.2 mg/kg) significantly inhibited the secondary cues-induced cocaine-seeking behavior. None of the above drugs significantly influenced the cue-controlled sucrose-seeking behavior. These results confirm the importance of the D3 as well as the D2 dopamine receptor in modulating the cue-induced cocaine relapse and the possible usefulness of the D3 dopamine receptor ligands as potential medication in cocaine addicts.
authors: Department of Behavioural Pharmacology, Gedeon Richter Ltd., P.O. Box 27, Budapest H-1475, Hungary. k.gal@richter.hu
authors: Krisztina
authors: K
authors: Gál
authors: István
authors: I
authors: Gyertyán
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects; D019970:Cocaine-Related Disorders / Q000517:prevention & control* / Q000523:psychology; D003463:Cues; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D050637:Receptors, Dopamine D3 / Q000187:drug effects*; D012054:Reinforcement, Psychology; D012646:Self Administration; D012932:Social Facilitation; D013395:Sucrose / Q000008:administration & dosage; D044005:Tetrahydroisoquinolines / Q000494:pharmacology
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D009570:Nitriles; D010879:Piperazines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C409982:SB 277011; D044005:Tetrahydroisoquinolines; C120565:BP 897; D013395:Sucrose; D006220:Haloperidol