[Effect of Catechol-O-methyltransferase deficiency on reinforcing effects of cocaine (experimental study)]

Catechol-O-methyltransferase (COMT) remains an important regulatory element in prefrontal cortex dopamine homeostasis. The literature data suggest that individual differences in COMT activity (Val158Met polymorphism) might have indirect downstream effects on the reward system. The aim of the present study was to examine whether COMT deletion affects reinforcing effects of cocaine in mice. The study was conducted in male mice with homozygous COMT deletion as well as their C57BL/6J wild-type littermates. Animals were trained to nose-poke to receive response-contingent intravenous infusions of cocaine (0.3 mg/kg per infusion; final schedule of reinforcement - fixed ratio (FR) 3 time out 30 s). Following the initial acquisition phase, cocaine self-administration dose-effect functions (0.03, 0.1, 0.3, 1, and 3 mg/kg per infusion) were determined under FR3 and progressive ratio (PR) schedules of reinforcement. Cocaine dose-dependently maintained responding under FR3 and PR schedule of reinforcement when the unit dose of cocaine was varied across the sessions. The total cocaine intake did not differ in COMT deletion mice and wild-type mice. The results of this study suggest that individual differences in COMT activity do not affect primary reinforcing effects of cocaine in mice.