The effects of morphine on the levels and release of acetylcholine (ACh) in the brain have been described. However, little information is available on the effects of morphine on ACh turnover. In addition, although there is a strong evidence that narcotics modify cholinergic mchanisms in the brain, the relationship of these changes to narcotic- induced analgesia or motor activity is unclear. We, therefore, propose to study the effects of acute and chronic administration of morphine on ACh turnover in brain and brain areas. ACh turnover will be estimated by measurement of the rate of decline of ACh following inhibition of choline acetylase and by measurement of ACh and choline specific activity through combined radio-pyrolysis gas chromatography. The effects of ACh receptor agonists and antagonists and cholinesterase inhibitors will be studied for their effect on morphine motor activity. These agents will also be administered in conjunction with morphine to animals pretreated with drugs that selectively inhibit biogenic amine systhesis in order to study their combined effect on morphine motor activity. Such an approach should allow us to correlate ACh turnover with observed motor effects and will help define the role of ACh in morphine effects and in neurohumoral regulation of motor activity. Such an approach should allow us to correlate ACh turnover with observed motor effects and will help define the role of ACh in morphine effects and in neurohumoral regulation of motor activity. The effect of alteration of cholinergic mechanisms on motor activity observed after chronic morphine treatment and the effect of chronic alteration of ACh on morphine tolerance development will be studied. Such data should provide valuable information on the role of ACh in the development of narcotic tolerance and physical dependence.