Tiospirone and the reinforcing effects of cocaine in the conditioned place preference paradigm in rats

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.