The overall goal of this research proposal is to investigate the neural mechanisms underlying the aversiveness of opioid withdrawal. In this project, behavioral experiments will be conducted to study the aversiveness of opioid antagonists micro injected into the nucleus accumbens of morphine dependent rats. Specifically, mu a and kappa selective opioid antagonists will be tested for conditioned place aversion, and the potential interaction between dopamine and this aversion will be tested. Concomitantly, in vitro brain slice techniques will be used to study the effects of opioid on the cellular properties of neurons from the shell of the nucleus accumbens. Furthermore, potential changes in these properties will be studied by preparing slices from morphine dependent rats. The results of these experiments should lead to an increased understanding of the specific neural circuitry involved in opioid withdrawal, which may be helpful in developing treatments for overcoming opioid addiction in humans.
