Dopaminergic involvement in the cocaine-induced up-regulation of benzodiazepine receptors in the rat caudate nucleus

Abstract

One group of 12 rats received discrete 6-hydroxydopamine (6-OHDA) injections into the caudate nucleus on one side of the brain and sham infusions on the other. Following chronic daily injections of cocaine (20 mg/kg, i.p.) or saline (1 ml/kg, i.p.) for 15 days, the caudate nuclei were separately dissected, and the number of benzodiazepine receptors labeled with [ 3H]Ro 15-1788 were assessed using individual homogenate receptor binding assays. A second group of 24 rats received bilateral infusions of 6-hydroxydopamine or sham infusions into the lateral ventricles followed by chronic cocaine or saline administration as described above. The animals were sacrificed by cardiac perfusion, and the brains were sectioned and prepared for light microscopic quantitative autoradiography. The extent of the lesion was assessed by measuring dopaminergic and noradrenergic uptake sites visualized with [ 3H]mazindol, while [ 3H]Ro 15-1788 was used to estimate the number of benzodiazepine receptors. Chronic cocaine administration resulted in significant increases in benzodiazepine receptors in the caudate nucleus, and these effects were attenuated following dopamine depletion. These data suggest that the effects of cocaine on benzodiazepine receptors may be mediated, in part, through the effects of the drug on dopaminergic neuronal activity.