ALTERED NEURONAL DISTRIBUTION OF PARVALBUMIN IN ANTERIOR CINGULATE CORTEX OF RABBITS EXPOSED IN-UTERO TO COCAINE

Previous studies of rabbits exposed in utero to cocaine have revealed an increase in the number of neurons which are GABA immunoreactive in the anterior cingulate cortex (ACC), suggesting a cocaine-elicited mod ification in the balance of excitatory and inhibitory interactions. Of the major calcium binding proteins expressed by different subgroups o f GABAergic neurons, parvalbumin has been observed in conditions invol ving excess excitation, and may serve to protect neurons from excitoto xicity. In the present study, we used immunocytochemistry to compare t he effects of prenatal cocaine exposure on the postnatal development o f parvalbumin immunoreactivity in interneurons of the visual cortex (V C) and ACC. We determined the number and laminar distribution of parva lbumin immunoreactive neurons, and we also assessed the distribution o f parvalbumin immunoreactivity within primary, secondary and tertiary dendrites of neurons in these two cortical areas. In both ACC and VC, parvalbumin immunoreactive neurons were first observed around postnata l day 10 (P10) and their number increased rapidly from P10 to P20. At all ages studied (P10 to P60) there was no difference between cocaine- exposed and saline control animals in the number or laminar distributi on of parvalbumin immunoreactive neurons in either cortical area. Howe ver, the distribution of parvalbumin immunoreactivity within dendrites revealed a significant difference between cocaine-exposed and saline control animals in ACC but not in VC. In ACC, at all ages studied, the re was an increase in the number of primary, secondary and tertiary de ndrites which were parvalbumin immunoreactive in cocaine-exposed anima ls compared with saline controls. This difference was most striking in secondary dendrites, and in laminae V and VI. The effect was observed at doses of 4 and 3 mg/kg per injection but not at 2 mg/kg per inject ion. In contrast to ACC, in VC there was no difference in the number o f immunoreactive dendrites in cocaine-exposed animals compared with sa line controls. These observations are consistent with the hypothesis t hat the ACC of rabbits exposed in utero to cocaine is characterized by altered excitatory/inhibitory interactions. ACC receives a dense dopa minergic input, but VC receives minimal dopaminergic innervation. Mech anisms by which the action of cocaine on the developing dopaminergic s ystem may modify the balance of excitation and inhibition in ACC are d iscussed.