Acute effects of benzodiazepines on operant behavior and in vivo receptor binding in mice

Lorazepam and alprazolam produced dose-dependent decreases in the rate of fixed-ratio (FR) 20 schedules of food presentation in which either a nose-poke or a lever-press defined the operant and under a fixed-interval (FI) 2-min lever-press schedule of food presentation. In contrast, under FI 2-min and differential reinforcement of low response rate (DRL) 20-s schedules of nose-poke responding for food, intermediate doses of alprazolam produced increases in response rate. Lorazepam, however, only decreased overall response rates under the FI schedule and produced some increases in responding under the DRL schedule. Acute in vivo benzodiazepine receptor binding experiments showed that low to intermediate doses of alprazolam produced significant increases in the binding of [3H]flumazenil in all brain areas tested, while lorazepam produced increases in the brain stem only. The acute effects on binding produced by both drugs were positively and significantly correlated with their acute effects on response rate only under the FR lever-press procedure. These results indicate that the effects of benzodiazepines on in vivo binding may be related to their effects on FR lever-press responding.