Microdialysis evidence that acetylcholine in the nucleus accumbens is involved in morphine withdrawal and its treatment with clonidine.

This study used microdialysis to measure changes in extracellular acetylcholine (ACh) content in the nucleus accumbens (NAC) of freely moving rats during acute and chronic morphine treatment, and following naloxone-precipitated withdrawal. Morphine injection (20 mg/kg, i.p.) caused a significant decrease in extracellular ACh which was not apparent after repeated exposure to the opiate for 7 days. Basal recovery of ACh was not altered by chronic morphine treatment. On day 8, after morphine dependence had been established, naloxone caused a large increase in ACh levels accompanied by withdrawal symptoms such as wet dog shakes, diarrhea and teeth-chattering. Pretreatment with clonidine (200 micrograms/kg, i.p.) reduced these withdrawal symptoms and eliminated the ACh response. These results suggest that accumbens ACh is involved in some of the aversive aspects of opiate withdrawal.