Cocaine-induced alterations in the density of monoaminergic receptors in the embryonic guinea pig cerebral wall

Quantitative receptor autoradiography was used to examine the effect of chr onic cocaine exposure on the density of alpha 1-, alpha 2- and P-adrenergic , 5-HT1A- and 5-HT2-serotonergic, and D1- and D2-dopaminergic receptors in the fetal guinea pig cerebral wall which contained forming motor area of th e cerebral cortex. The pregnant guinea pig received two daily subcutaneous injections of 20 mg/kg cocaine beginning on the 20th day of pregnancy (E20) . The control animals received injections of equivalent volume of saline. T he receptor densities were examined between days 5-30 of the treatment, whi ch corresponds to E25-E50. By the fifth day of treatment (E25), cocaine pro duced downregulation of all receptors studied throughout the entire depth o f the fetal cerebral wall. More extended treatment, however, resulted in re covery of receptor levels. Finally, from days 20-30 of treatment (E40-E50) there was a significant upregulation of noradrenergic and dopaminergic rece ptor sites. These findings demonstrate that exposure to cocaine in utero ca n influence adrenergic, serotonergic, and dopaminergic receptors in the emb ryonic cerebral wall, which may lead to alteration in corticogenesis. Furth ermore, the present study reveals that, in the course of chronic treatment, cocaine may completely reverse its receptor regulatory activity in the fet al brain. (C) 1999 Wiley-Liss, Inc.