The proposed project builds upon previous studies of the neuronal interaction between cocaine and buprenorphine. In those experiments, under acute conditions, the investigators found that buprenorphine itself produced more complex effects than cocaine and dopaminergic compounds. This was not surprising in view of the complex agonistic potential of buprenorphine, and their studies showed that both dopamine and opioid receptor systems are implicated in the drug's actions. Studies on the interaction of buprenorphine with cocaine revealed a significant attenuation of acute cocaine-elicited depression by buprenorphine. However, excitation following cocaine was resistant to any buprenorphine influence. In order to confirm, extend, and eventually apply these findings in the context of cocaine dependence, two parallel studies are proposed. One of these would probe the possible GABA and opiodergic mechanisms underlying the actions and interactions of the two drugs; the second would extend this to cocaine-dependent animals. Specific objectives include: (1) Characterizing neuronal responsiveness to intravenous cocaine as a function of dose; (2) Determining dose-related responses of neurons to GABAergic agonists and antagonists; (3) Analyzing neuronal responses to opioid agonists and antagonists; (4) Investigating whether a given neuron can be both GABA- and opioid-receptive; (5) Characterizing neuronal interaction of GABA and cocaine; (6) Characterizing the influence of opiates on cocaine actions; and (7) Determining if GABAergic and opiodergic mechanisms mediate or otherwise influence cocaine actions interactively.
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