INTRAUTERINE COCAINE EXPOSURE OF RABBITS - PERSISTENT ELEVATION OF GABA-IMMUNOREACTIVE NEURONS IN ANTERIOR CINGULATE CORTEX BUT NOT VISUAL-CORTEX

The effects of prenatal cocaine exposure on the development of the rab bit cerebral cortex were studied. Two cortical areas were compared: pr imary visual cortex (VC) and anterior cingulate cortex (ACC). ACC was selected because behavioral deficits observed in cocaine-exposed infan ts suggest the involvement of ACC. In addition, ACC receives dense dop aminergic innervation and cocaine's action in inhibiting the re-uptake of dopamine is believed to underly the rewarding properties of cocain e. VC was selected as a control area because there is no evidence of b ehavioral deficits associated with visual perception in cocaine-expose d infants, and because VC receives minimal dopaminergic innervation. T wo aspects of cortical development were studied: (i) cortical morpholo gy, growth and cytoarchitectonic organization; and (ii) the developmen t of the GABAergic neurotransmitter system. Measures of postnatal cort ical growth, including cortical lamination, cell number and soma size, were compared in cocaine-exposed or control (saline) rabbits aged P5- P60. There was no difference between cocaine and saline animals in any of these parameters, and cortical cytoarchitecture appeared normal. H owever, despite the absence of major abnormalities in cortical develop ment, we found that the number of GABA-immunoreactive neurons in cocai ne-exposed animals was significantly higher than normal in ACC. This e ffect was highly consistent, was present in all laminae and at all age s studied, and persisted into maturity (P60). In contrast, in VC, the number of GABA-immunoreactive neurons in cocaine-exposed animals did n ot differ from normal. We suggest that increased GABA immunoreactivity may reflect a compensatory response to excessive excitatory input to ACC. A change in the balance of excitation and inhibition in ACC, refl ecting 'noisy' or dysfunctional intracortical circuitry, may underly t he emotional lability and attentional deficits characteristically desc ribed in infants exposed in utero to cocaine.