Sexual dimorphism in the brain metabolic response to prenatal cocaine exposure

The effects of prenatal cocaine exposure on the metabolic function of major central neuronal systems in the periweanling rat are reported in this study. Pregnant Sprague--Dawley rats were administered cocaine at either 30 or 60 mg/kg or the vehicle from gestation day (G) 8 through 22 via daily gastric intubation. Since prenatal cocaine has been shown to alter behavior in weanling rats, brain functional activity was quantified using the deoxyglucose method in male and female 21-day-old offspring (one of each gender/litter). Cocaine's effects were most significant within the limbic system where a three-way interaction between cocaine treatment, sex and brain region was seen. Within the limbic system, two regions, the rostral accumbens and the diagonal band of Broca showed reductions in metabolic activity in the exposed male offspring compared to the control offspring while no changes were seen in females. At more caudal levels of the forebrain, the accumbens (at the level of 1.2 micro rostral to Bregma) and septum showed cocaine-induced reductions in metabolism which were not dependent upon the sex of the animal. Metabolism within the hypothalamus also tended to show a significant interaction between treatment, gender and brain region (P=0.06). Two regions, including the ventromedial nucleus and lateral hypothalamic area, were metabolically depressed in the males alone while three other regions; the dorsomedial, arcuate, and medial preoptic nuclei were also metabolically depressed in the treated groups collapsed across gender. There were no significant treatment or sex-related effects or interactions within the sensory and motor systems. Chronic prenatal cocaine exposure reduced metabolism significantly in a restricted portion of the forebrain, the mesocortical-limbic system, particularly in regions associated with the medial forebrain bundle. These reductions were seen primarily in males while some regions showed changes which were independent of the sex of the animal. These cocaine-induced effects resembled, to a great extent, those seen in similarly-treated males examined as adults. The data emphasize that cocaine use during a restricted period of early pregnancy depresses function within limbic and hypothalamic regions and that many of these effects are sexually dimorphic in nature.