alexa Effects of SCH 23390 and eticlopride on cocaine-seeking produced by cocaine and WIN 35,428 in rats.


Journal of Addiction Research & Therapy

Author(s): Schenk S, Gittings D

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Abstract 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. This article was published in Psychopharmacology (Berl) and referenced in Journal of Addiction Research & Therapy

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