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 D1- and D2-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 D1-like antagonist, SCH 23390 (0.001–0.010 mg/kg) or the D2-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 D2 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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Acknowledgements.
This research was supported by DA 10084. The technical assistance of Carol McNamara is gratefully acknowledged.
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Schenk, S., Gittings, D. Effects of SCH 23390 and eticlopride on cocaine-seeking produced by cocaine and WIN 35,428 in rats. Psychopharmacology 168, 118–123 (2003). https://doi.org/10.1007/s00213-002-1276-y
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DOI: https://doi.org/10.1007/s00213-002-1276-y