The present research project is to conduct further studies on the involvement of gamma-aminobutyric acid (GABA) system in morphine analgesia, tolerance and physical dependence. The research plan includes (1) to study the GABAergic modulation of morphine binding site sensitivity in vitro by using brain synaptosomal preparations and synaptosomal plasma membranes in naive and morphine tolerant-dependent mice; (2) to study the high-affinity uptake properties of GABA during the development of morphine tolerance and after withdrawal in rodents; (3) to study the release properties of GABA in vitro in synaptosomes and synaptic vesicles from the whole brain and various regions of the brain in non-tolerant and tolerant-dependent animals in the presence and absence of morphine or its antagonists; and (4) to study the microcomplement fixation tests of two key enzymes on GABA metabolism, L-glutamate decarboxylase (GAD) and GABA-transaminase (GABA-T) in homogenates of whole brain, discrete areas of the brain and synaptosomes obtained from the mouse during the process of development of morphine tolerance and after withdrawal. The information obtained from this project hopefully will provide a clearer scheme of the involvement of GABA system in morphine addiction and furnish a more rational basis for the treatment of morphine addiction in humans.