COCAINE DISRUPTION OF MATERNAL BEHAVIOR--RODENT MODELS

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Clearly it is not possible to rigorously prove that cocaine alteration of brain mechanisms even partly underlies poor parenting found in cocaine abusing women since determination that cocaine is an independent risk is quickly confounded by the presence of many other risk factors. Therefore we propose to examine whether there is a cocaine-mediated derailment of maternal behavior in a well characterized laboratory model, the rat, and to examine the neurobiological basis of this affect. Specific Aim I. Does cocaine interfere with the onset of maintenance of normal maternal behavior in the rat? The effect of cocaine on maternal behavior that is the natural outcome of pregnancy will be examined using the controlled administration with an Alzet osmotic minipump. Since the self-administration of cocaine in a binge regime has been documented for humans, we wish to examine the possibility that a self-administered binge regime might interfere with maternal behavior more consequently than does the constant administration paradigm. The dosages will range a log order in magnitude and remain below the doses known to induce convulsions or to be grossly teratogenic. Should any cocaine-induced parturition difficulties arise we will use Caesarean delivery of pups, since the experience of parturition is not required for pregnancy-induced maternal behavior. Specific Aim II. Does cocaine alter the estrogen and progestin receptors in brain regions key to the onset of maternal behavior, and could this underlie cocaine altered maternal behavior? The central command post of the maternal response is the subset of estrogen and progestin sensitive neurons in the preoptic area of the brain. We propose that if cocaine interferes with the normal onset or complete display of maternal behavior it may be doing so by affecting the steroid hormone receptors in these neurons. We will document cocaine effects on steroid hormone receptors in neurons that are key to the maternal response using immunocyto-chemistry with antibodies directed against estrogen and progestin receptors. No workers who have been the principal architects of our understanding of maternal behavior in rats have approached this problem. Our main contribution to this difficult and complex problem is that we have experience examining maternal behavior and its neurobiological basis. Neither of us has had research experience with any aspect of the neural or behavioral effects of drugs of abuse. We seek these funds to expand our research capacity into a new area.