Comparison of the effects of scopolamine and methylscopolamine on the performance of a fixed-ratio discrimination in squirrel monkeys.

In the presence of a stimulus behind the center key, squirrel monkeys were required to complete one of two fixed ratios (FRs) on the center key (FR 30 or FR 25). Completion of the ratio turned off the center-key stimulus and produced a stimulus behind each of the two side keys. If the completed ratio was high (e.g., FR 30), a response on the left key produced a food pellet. If the ratio was low (e.g., FR 25) a response on the right key produced food. Errors produced a brief timeout. Dose-effect curves for scopolamine (0.001-0.18 mg/kg) and methscopolamine (0.0032-5.6 mg/kg) were determined under a FR 30 vs. FR 25 discrimination, which controlled both moderate levels of accuracy and high rates of responding. Scopolamine produced a dose-related decrease in overall response rates and increase in percent errors. Methscopolamine decreased response rates and increased percent errors in a dose-related manner much like scopolamine. However, scopolamine was found to be about 10 times more potent on a mg/kg basis than methscopolamine. Scopolamine is in general considered to be centrally acting due in part to its lipid solubility. The results from these studies suggest that methscopolamine, in general considered to be peripherally acting, may also cross the squirrel monkey blood-brain barrier at high doses and produce behavioral effects comparable to those of scopolamine.