Effects of scopolamine and methscopolamine on acquisition and retention of rat one-way shuttle box behavior and total brain acetylcholine.

The effects of scopolamine HBr (0.032 to 10.0 mg/kg), methscopolamine Br (1.0 and 10.0 mg/kg) and 0.36 mg/kg NaBr on acquisition and retention of one-way avoidance behavior and total brain acetylcholine (ACh) were studied in male albino rats. Compared to equimolar NaBr, scopolamine caused a dose-related impairment in acquisition of avoidance responding while methscopolamine did not. Retention of avoidance behavior in trained rats was also disrupted, but the detrimental effect was smaller and occurred only following large doses of scopolamine. The per cent escape behavior was not decreased by any of the treatments. It increased as avoidance was decreased. Scopolamine caused a dose-related increase in latency and avoidance and escape responding compared to equimolar NaBr. However, scopolamine increased the latency of avoidance at lower doses and to a greater degree than it increased the latency of escape. Escape latencies were significantly increased only at the largest dose (10 mg/kg). These dose-related effects of scopolamine were greater during acquisition than during retention. Small doses (0.032 mg/kg) shortened latency of avoidance during retention. Methscopolamine increased avoidance and escape latencies only at the largest dose (10 mg/kg). Scopolamine produced a dose-related decrease in brain ACh which correlated well with the per cent avoidance in acquisition (r = 0.95) and retention (r = 0.88) trials. It is concluded that a muscarinic cholinergic antagonist with central actions like scopolamine affects selective aspects of avoidance behavior in low doses, and that these changes are highly correlated with brain ACh levels.