Effects of Catechol-O-Methyltransferase Deficiency on the Reinforcing Effects of Cocaine (an experimental study)

The effects of catechol-O-methyltransferase deficiency on sensitivity to the reinforcing action of cocaine were studied in male C57BL/6J mice with knockout of the COMT gene and wild-type mice of the same generation. Animals were trained to peep into an opening to receive intravenous infusions of cocaine (0.3 mg/kg per infusion; the reinforcement regime had a fixed reward:reinforcement ratio of 3:1 (FR3) and a 30-sec time-out). After the initial response acquisition phase, reinforcement in the FR3 regime and an increasing ratio (IR) regime was used to plot dose-effect curves for cocaine (0.03, 0.1, 0.3, 1, and 3 mg/kg per infusion). Cocaine self-administration reactions showed a relationship between dose and effect, total cocaine consumption in the FR3 and IR regimes being similar in mice of the two types. These results lead to the conclusion that individual differences in COMT activity do not affect the sensitivity of mice to the primary reinforcing action of cocaine.