Altered neuronal distribution of parvalbumin in anterior cingulate cortex of rabbits exposed in utero to cocaine.

ABSTRACT

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 modification in the balance of excitatory and inhibitory interactions. Of the major calcium binding proteins expressed by different subgroups of GABAergic neurons, parvalbumin has been observed in conditions involving excess excitation, and may serve to protect neurons from excitotoxicity. In the present study, we used immunocytochemistry to compare the effects of prenatal cocaine exposure on the postnatal development of parvalbumin immunoreactivity in interneurons of the visual cortex (VC) and ACC. We determined the number and laminar distribution of parvalbumin immunoreactive neurons, and we also assessed the distribution of 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 postnatal 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 distribution of parvalbumin immunoreactive neurons in either cortical area. However, 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, there was an increase in the number of primary, secondary and tertiary dendrites which were parvalbumin immunoreactive in cocaine-exposed animals 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 injection. In contrast to ACC, in VC there was no difference in the number of immunoreactive dendrites in cocaine-exposed animals compared with saline controls. These observations are consistent with the hypothesis that the ACC of rabbits exposed in utero to cocaine is characterized by altered excitatory/inhibitory interactions. ACC receives a dense dopaminergic input, but VC receives minimal dopaminergic innervation. Mechanisms by which the action of cocaine on the developing dopaminergic system may modify the balance of excitation and inhibition in ACC are discussed.