Alterations in striatal acetylcholine,acetylcholine esterase and dopamine after methadone replacement in morphine-dependent rats

Chronic treatment of rats with morphine was found to produced a significant increase in endogenous ACh and DA as well as a decrease in AChE activity of rat striatum. Narcotic withdrawal for 48 hr resulted in a reversal of morphine-induced changes in striatal ACh levels and AChE activity whereas the enhanced striatal DA remained unaltered. Methadone replacement failed to affect the changes in striatal ACh and AChE activity but abolished the increases in striatal DA seen in morphine-withdrawn rats. Our results suggest that ‘morphine addiction’ in rats may involve alterations in the cholinergic and dopaminergic mechanisms of the striatum and that methadone replacement influences primarily the changes in the dopaminergic system produced by chronic morphine and its subsequent withdrawal.