Accelerated resensitization of the D1 dopamine receptor-mediated response in cultured cortical and striatal neurons from the rat: respective role of alpha 1-adrenergic and N-methyl-D-aspartate receptors.

As previously shown in vivo, noradrenergic and glutamatergic neurons can regulate the denervation supersensitivity of D1 dopaminergic (DA) receptors in the rat prefrontal cortex and striatum respectively. Therefore, the effects of methoxamine (an alpha 1-adrenergic agonist) and glutamate on the resensitization of D1 DA receptors were investigated in cultured cortical and striatal neurons from the embryonic rat. In the presence of sulpiride and propranolol, DA stimulated the D1 DA receptor-mediated conversion of 3H-adenine into 3H-cAMP in both intact cortical and striatal cells and these responses were markedly desensitized in cells preexposed for 15 min to DA (50 microM). The complete recovery of the D1 DA response was more rapid in striatal (15 min) than in cortical (80 min) neurons. Methoxamine accelerated the resensitization of the D1 response in cortical but not in striatal neurons. The effect of the alpha 1-adrenergic agonist in cortical neurons was blocked by prazosin and chlorethylclonidine. In contrast, glutamate accelerated the resensitization of the D1 response in striatal but not in cortical neurons and the effect observed in striatal neurons was totally blocked by 2-amino-5-phosphonovaleric acid, an NMDA receptor antagonist. Protein kinase C was shown to be involved in the alpha 1-adrenergic-induced resensitization of the cortical D1 response but not in the glutamate-evoked resensitization of the striatal D1 response. Finally, for comparison, similar experiments were performed on beta-adrenergic receptors using isoproterenol (1 microM) as an agonist. Methoxamine did not modify the resensitization of the beta-adrenergic response in cortical neurons, but glutamate accelerated the resensitization of this response in striatal neurons.