Tiospirone and the reinforcing effects of cocaine in the conditioned place preference paradigm in rats
Arolfo MP, McMillen BA
Center for Alcohol and Drug Abuse Studies,
Department of Pharmacology,
Brody School of Medicine at East Carolina University,
Greenville, NC 27858, USA.
J Pharm Pharmacol 2000 Aug; 52(8):977-81


Tiospirone (TSP) is an atypical antipsychotic drug. It has 5HT-2 antagonistic properties as well as affinity for D2, 5HT-1a, 5HT-6 and sigma receptors. Behavioural studies in our laboratory, which used a 24h free access to food and fluids paradigm, showed a decreased alcohol and increased food intake after twice-daily administration of TSP; the maximal effect was obtained at a dose of 0.48 mg kg(-1). This study used the conditioned place preference paradigm to determine the effect of TSP on the reinforcing properties of cocaine. Intraperitoneal administration of 5.0 mg kg(-1) cocaine, but not saline, increased the time rats spent in the drug-paired compartment of a three-compartment shuttle box by 104.9%. Two doses of TSP, 0.143 and 0.48 mgkg(-1), were tested subcutaneously 60 min before saline or cocaine administration during the conditioning phase only. A dose-response effect was observed with a significant reduction in the time rats spent in the cocaine-paired compartment on the drug-free test day produced by the dose of 0.48 mg kg(-1) (an increase of only 38.1% when post-conditioned times were compared with preconditioned times). These findings suggest that TSP reduces the reinforcing properties of cocaine exhibited in the conditioned place preference paradigm.

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