The present proposal is designed to continue ongoing work in our laboratory directed at exploring the neuronal pathways and neurochemical substrates involved in opiate reinforcement and dependence. The overall hypothesis being tested is that a common neural substrate mediates the reinforcing and dependence inducing properties of opiates relevant to drug abuse. Work in the previous funding period has led to a focus on the region of the nucleus accumbens and its connections in the positive reinforcing effects of opiates and in the negative reinforcing effects of opiate withdrawal. The experiments outlined in the present proposal will identify the neural sites important for the reinforcing properties of opiates in dependent rats and compare this information to that already generated in the non-dependent animal. Neural sites important for various opiate withdrawal responses including response-suppression aversion and unconditioned behavior will be identified using local intracerebral injections of a quaternary derivative of naloxone in dependent rats. Significant evidence exists to show that rats, monkeys and man show behavioral and physiological manifestation of a conditioned opiate withdrawal where previously neutral stimuli that have been paired with a state of precipitated withdrawal response. An attempt will be made to produce a rat model of conditioned withdrawal and to define the motivational properties of such conditioned stimuli in drug self- administration. Finally the role of afferents to the nucleus accumbens in opiate reinforcement and dependence will be examined with a focus on the amygdala accumbens projection. These studies have important implications for our understanding of the neural substrates involved in opiate seeking behavior and the drug abuse process.
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