Human studies of children exposed to cocaine prenatally reveal a constellation of effects which include altered attention, affect, arousal regulation and cognitive function. While the effects often differ depending on the sex of the individual, no studies to date have investigated the effects of prenatal cocaine exposure on drug-taking behaviors in female and male offspring. Others have found that postnatal environment plays a role in the manifestation of the effects of many in utero exposures. Since animal studies can differentiate the biological effects of prenatal cocaine exposure from the effects of postnatal environment, we propose to examine the role of postnatal environment in the manifestation of prenatal cocaine effects in male and female offspring. Studies will parallel the clinical projects which are examining drug taking behavior in adolescent male and female subjects exposed to cocaine prenatally.
Aim 1 : to determine the role of prenatal cocaine exposure in the function of reward circuits in female and male adolescent rats. Prenatally exposed male and female rats will be tested for conditioned place preference (CPP) as adolescents following rearing in an impoverished or a moderately enriched environment.
Aim 2 : to determine the role of prenatal poly-drug exposure along with cocaine in the development of the reward circuits in male and female rats. The effects of prenatal nicotine, THC and alcohol along with cocaine on CPP for cocaine will be determined in female and male adolescents.
Aim 3 : to determine the biological basis for the sex differences in reward circuits using functional imaging techniques and neurochemical assessments. Studies will be carried out in subjects treated as in Aims 1 &2 which show the greatest effects of prenatal cocaine in female and male adolescents undergoing CPP. Following CPP training with a dose of cocaine found to differentiate the prenatal cocaine subjects from the controls, functional imaging studies will be carried out on the test day to visualize the circuits activated by the drug cue. Other rats at 50 days of age will be sacrificed without undergoing CPP and the brains sent to U. Miami for neurochemical assessments. Together these studies will determine the influence of two major confounders in clinical studies (environment and poly- drug use)on the effects of prenatal cocaine exposure emphasizing the differences/similarities of male and female subjects in drug taking behavior using an appropriate preclinical model.
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