Cocaine has complex pharmacologic actions which may operated individually or collectively to produce long term neurochemical and neurobehavioral alterations in offspring of cocaine using women. This proposal will examine one of the major pharmacologic actions of cocaine: the local anesthetic effects. By examining the local anesthetic effects of cocaine as they interact with the developing nervous sytem, we will be closer to understanding the mechanisms of cocaine's developmental toxicity. First, the local anesthetic effects of cocaine will be examined for developmental toxicity (AIM 1). Lidocaine, which has a similar analgesic potency as cocaine, will be given to rats during development and compared to both control and cocaine exposed rats. Similarities and differences between equivalent doses of the two compounds will be determined using measures of brain functional activity (deoxyglucose and iodoantipyrine) receptor binding autoradiography, activity, startle-reflex and response to pharmacological challenge. These studies will incorporate nontreated and pair-fed controls, foster all prenatally exposed pups to nontreated dams, and collect maternal toxicity data. By identifying the similarities between the developmental toxicity of cocaine and lidocaine, we will enhance out understanding not only about how cocaine produces abnormal development, but also about basic developmental processes. These studies will ultimately provide an understanding of the risk associated with cocaine use during pregnancy.
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