Abstract

Two inhibitors of acetylcholinesterase, physostigmine and diisopropylfluorophosphate, potentiated morphine antinociception, as measured by inhibition of the tail-flick response, in both nontolerant mice and in mice rendered tolerant to morphine by pellet implantation for three days. Although the response to morphine was modified in tolerant animals, inhibition of acetylcholinesterase did not alter the development of tolerance. Physostigmine and diisopropylfluorophosphate also caused pronounced inhibition of naloxone-precipitated withdrawal jumping; however, development of physical dependence on morphine, as measured by body weight loss during abrupt withdrawal, was not affected by the two drugs. These results suggest that some of the actions of morphine might be mediated in part by acetylcholine and, although acetylcholinesterase inhibition may modify the tolerant and dependent state, the mechanism involved primarily in their development is not materially affected.