Changes in the activity of acetylcholinesterase (AChE) of the isolated vas deferens from normal, castrated, morphine and ethanol-tolerant rats were studied. Three days after the termination of treatment with morphine and on the last day of treatment with ethanol, a significant inhibition of the activity of AChE was detected. This reduction in the enzymatic activity persisted in morphine-tolerant rats for 15 days, but not for 30 days, at which time the levels of AChE were determined to be normal. However, in ethanol-tolerant rats, there were no significant changes found at days 15 or 30. The activity of AChE was decreased significantly in castrated rats, but this effect was reversed by treatment with testosterone. During withdrawal from morphine or ethanol, the levels of AChE were significantly increased. The results indicate that morphine and ethanol may be inducing changes in the feedback mechanism which regulates the levels of AChE at post-synaptic sites, and these changes could play an important role in the development of tolerance to morphine and to ethanol.
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