期刊
PSYCHOPHARMACOLOGY
卷 168, 期 1-2, 页码 118-123出版社
SPRINGER-VERLAG
DOI: 10.1007/s00213-002-1276-y
关键词
relapse; cocaine-seeking; cocaine; WIN 35,429; dopamine; SCH 23390; eticlopride
资金
- NIDA NIH HHS [DA 10084] Funding Source: Medline
Rationale.. Exposure to a small amount of cocaine can trigger relapse, and so an understanding of the mechanisms underlying cocaine-seeking are important for the development of effective anti-relapse treatments. Objectives.. The present study sought to compare the contributions of dopamine D-1- and D-2-like receptors in drug-seeking produced by cocaine and WIN 35,428. Methods.. Reinstatement of extinguished cocaine self-administration was measured for rats that received injections of cocaine (5.0-20.0 mg/kg) or WIN 35,428 (0.1-1.0 mg/kg) following extinction. Prior to the injection of cocaine or WIN 35,428, rats received an injection of the D-1-like antagonist, SCH 23390 (0.001-0.010 mg/kg) or the D-2-like antagonist, eticlopride (0.01-0.30 mg/kg). Effects of SCH 23390 (0.01 mg/kg) on cocaine-produced locomotor activation were also measured in separate groups of rats. Results.. The ability of both cocaine and WIN 35,428 to produce cocaine-seeking was dose-dependent. Within the range of doses tested, SCH 23390 failed significantly to attenuate the ability of either cocaine or WIN 35,428 to reinstate extinguished cocaine self-administration, although cocaine-produced locomotor activation was significantly attenuated by pretreatment with the highest dose of SCH 23390. Eticlopride attenuated both cocaine and WIN 35,428 produced cocaine-seeking but lower doses were required to decrease WIN 35,428-produced cocaine-seeking. Conclusions.. These results suggest that dopamine D-2 mechanisms are involved in cocaine-seeking produced by both cocaine and WIN 35,428. The lower potency of eticlopride in attenuating cocaine-produced cocaine-seeking suggest that cocaine's effects at sites other than the dopamine transporter contribute to its ability to elicit drug-seeking.
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