The work outlined in this proposal will examine further the neurobehavioral consequences of gestational exposure to cocaine administered subcutaneously (s.c.) in Sprague-Dawley rat pups. In work conducted during the previous funding period, psychopharmacological and behavioral evidence was obtained consistent with the hypothesis that gestational cocaine exposure may result in an attenuation in dopamine (DA) activity, at least during the preweaning period. Young offspring exposed gestationally to cocaine were also observed to exhibit cognitive deficits in some but not all conditioning situations. The research outlined in this proposal will investigate further these apparent alterations in DA function and cognitive performance seen early in life following gestational cocaine exposure in Sprague-Dawley rate. Gavid dams will be s.c. injected daily with 10, 20 94 40 mg/kg/3cc cocaine hydrochloride from gestational day 8 (E8) to E20. Control groups include dams similarly injected with 0.9% saline and pair-fed to the 40 mg/kg cocaine dams, as well as non-treated dams. Offspring from all groups will be fostered to surrogate dams on postnatal day 1.
In Specific Aim 1, DA function will be examined in offspring from these prenatal treatment groups throughout ontogeny in terms of assessment of DA metabolism (as an index of DA turnover), responsiveness to pharmacological challenges with apomorphine and haloperidol (using psychopharmacological, neurochemical and hormonal response measures), and examination of DA autoreceptor function.
In Specific Aim 2, studies will examine the circumstances under which cognitive deficits are observed in neonatal, infant, weanling, periadolescent and adult offspring exposed gestationally to cocaine to determine whether observed deficits in conditioning and retention are related to degree of training, the sensory modalities used for conditioned stimuli, the type of unconditioned stimulus used for conditioning, and the type of response measure used for assessment of performance. Studies will also be conducted to assess whether disruptions in cognitive performance seen early in life are related to maturational delays in cognitive development, or to alterations in cognitive function per se. Such animal research examining the neurobehavioral consequences of early cocaine exposure is particularly important at this time, given the recent escalation in the number of human offspring exposed gestationally to cocaine.
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