The program considers effects of morphine on the brain and adenohypophysis which may contribute further understanding to the mechanism involved in the development of tolerance or dependence to morphine utilizing the following experimental models in rats. 1. Effect of blocking the response to morphine on protein synthesis of the CNS with naloxone. 2. The effect of low doses of morphine (said to be stimulatory) on protein synthesis in CNS cortical protein or in various neurons. 3. Disc gel electrophoresis of CNS proteins in control, morphine-treated and in animals undergoing withdrawal from morphine. 4. A autoradiographic analysis of the distribution of labeled amino acids using the freeze-dried method of Stumpf to demonstrate bound and free amino acids as compared to results obtained by standard radioautographic procedures. This should permit an evaluation of the effect of morphine on the free amino acid pool in neurons and neuropil. 5. Preliminary electronmicroscopy studies demonstrating changes in the endoplasmic reticulum in arcuate nucleus neurons, will be extended to include the effects of withdrawal and of agents which interfere with biogenic amines. Morphine effects on the developing and adult pituitary, as well as on muscle will be undertaken in view of reports of altered trophic hormone production in morphine-treated animals utilizing electronmicroscopic and histochemical procedures.