COCAINE ADMINISTRATION IN PREGNANT RABBITS ALTERS CORTICAL STRUCTURE AND FUNCTION IN THEIR PROGENY IN THE ABSENCE OF MATERNAL SEIZURES

Previous studies have reported that cocaine exposure in utero results in structural and functional alterations in the development of the ant erior cingulate cortex (ACC). In the present study, the effects of mat ernal cocaine dosage and of cocaine-elicited maternal seizures on the progeny were studied. The incidence of maternal generalized tonic clon ic seizures (GTCSs) elicited by cocaine was recorded. No GTCSs were el icited in pregnant rabbits by doses of 2 or 3 mg/kg of cocaine, but GT CSs were sometimes elicited by the highest dose (4 mg/kg per injection ). We analyzed the offspring of cocaine-exposed and control animals us ing three assays of ACC development: (i) the structure of apical dendr ites of pyramidal neurons, (ii) the distribution of a calcium binding protein (parvalbumin) in the dendrites of GABAergic neurons, and (iii) coupling of D-1-like receptors and their G proteins. In all progeny o f rabbits exposed to 3 or 4 mg/kg of cocaine during pregnancy, there w as a significant change in the structure of apical dendrites, a signif icant increase in the number of dendrites of GABAergic neurons which w ere parvalbumin immunoreactive, and a significant reduction in D-1/G p rotein coupling, In assays of apical dendrites, the effects on offspri ng of rabbits given 2 mg/kg cocaine were as pronounced as in offspring of rabbits given 3 or 4 mg/kg, but the effects on parvalbumin immunor eactivity and D-1/G protein coupling were reduced at this low dose, Th us, previous findings of ACC developmental abnormalities in offspring of rabbits given a dose of 4 mg/kg were replicated, the effects were s hown to be dose-related and to be independent of maternal seizures. A mechanism by which dysfunction of the D-1 receptor system could mediat e cocaine-associated changes in all three parameters of ACC structure and function is discussed.