Morphine dependence and in vivo turnover of acetylcholine in whole mouse brain

Turnover rates of acetylcholine (ACh) were estimated in mouse brain after intravenous injection of phosphoryl(Me-14C)choline by applying principles of steady-state kinetics to the change with time of choline and ACh specific radioactivities. Turnover rate of brain ACh was estimated: 1) 45 minutes after a single injection of morphine (350 mumol/kg); 2) 3.5 days after implantation of a morphine pellet (250 mumol/pellet); 3) 15 minutes after 24 mumol/kg of naloxone to precipitate withdrawal in mice implanted with morphine pellets for 3.5 days; and 4) 15 minutes after 24 mumol/kg of naloxone. Brain ACh turnover rate was unchanged in mice that were given a single injection of morphine but was increased significantly in mice that had been made physically dependent upon morphine. During naloxone-precipitated withdrawal, the brain ACh turnover rate was found to be equal to that of mice treated only with naloxone.