Brain acetylcholine and choline following acute and chronic morphine treatment and during withdrawal

Levels of brain acetylcholine and choline were measured with a gas chromatograph in Swiss-Webster or ICR mice and Sprague-Dawley rats: a) 30 minutes after various single doses of morphine sulfate s.c.; b) rendered highly tolerant to and dependent on morphine by pellet implantation for 3 days; c) at various times after abrupt withdrawal (pellet removal); or d) during abstinence precipitated by the narcotic antagonist naloxone. The specific activity of brain acetylcholinsterase was determined in treatment d. Brain choline levels generally remained unaffected by the above manipulations. It was found that analgetic doses of morphine did not alter the steady-state levels of brain acetylcholine, but slight increases were observed after high doses and in morphine-tolerant animals. Abrupt withdrawal of morphine in the mouse caused a significant increase in brain acetylcholine levels, which was observed at 6 hours but not at 12 and 24 hours. In rats, abrupt withdrawal had no effect on acetylcholine levels at 6 and 18 hours. Nalonone-precipitated withdrawal significantly lowered the brain acetylcholine in both mice and rats without affecting acetylcholinesterase activity. This lowering was observed in animals that jumped after naloxone, but not in those failed to jump. It is concluded that this decrease in brain acetylcholine may be related to an increased neuronal release.