We are concerned with the role of neuroregulatory agents in the biological processes which underlie cocaine abuse. We would plan a five-pronged investigation of the problem: 1. Examine the manner in which cocaine alters the levels, metabolites, synthesis, turnover and metabolic pathways of potential neurotransmitters including serotonin, norepinephrine, and dopamine. We would also examine changes in the secondary messenger, cyclic AMP. 2. Study the dynamic changes induced by acute and chronic cocaine treatment on synaptosomal regulation of amine synthesis, uptake and release, and also determine changes in the activity and levels of the enzymes involved in amine synthesis. 3. Through the use of implanted push-pull cannula, determine the release of the aforementioned amines and of acetylcholine in intact conscious animals which had been treated with cocaine. Such studies would permit analysis through time in the same animal. 4. Monitor the levels of cocaine in treated preparations through the use of mass spectrometric (mass fragmentography) techniques. 5. Compare the effects of cocaine with those of morphine. Through these interrelated studies of the basic mechanisms of cocaine, we would hope to obtain information relevant to an understanding of the compound as a drug of abuse.