Alteration of dopamine transport in the striatum and nucleus accumbens of ovariectomized and estrogen-primed rats following N-(p-isothiocyanatophenethyl) spiperone (NIPS) treatment

The ability of N-(p-isothiocyanatophenethyl) spiperone (NIPS, 10 mg/kg, 24 h), a selective, irreversible alkylating agent of the dopamine D-2 receptor , to alter properties of dopamine uptake and clearance in the striatum and nucleus accumbens of ovariectomized and estrogen-primed (estradiol benzoate , 10 mug, 48 h, 24 h) rats was examined using voltammetry, The effectivenes s of NIPS was evaluated independently by measuring agonist mediated potenti ation of [S-35]-guanosine 5 '-(gamma -thiotriphosphate) ([S-35]-GTP gammaS) binding and [H-3]-dopamine uptake. A decrease in E-max for ligand potentia ted [S-35]- GTP gammaS binding and a loss of quinpirole potentiated [H-3]-d opamine uptake was observed consistent with a NIPS mediated alkylation and functional down-regulation of the dopamine D-2 receptor. This down-regulati on was associated with an attenuation of the dose dependent uptake of dopam ine in both the striatum and the accumbens, Go-administration of estrogen a nd NIPS resulted in a further attenuation of dopamine potentiated [S-35]-GT P gammaS binding measured in vitro and dopamine uptake measured in vivo. An alysis of the voltammetric profile revealed that clearance and T-50 times w ere significantly prolonged in animals treated with estrogen and NIPS compa red with those treated with NIPS alone. These data are consistent with both a steroid mediated impairment in dopamine autoreceptor/dopamine transporte r coupling and an independent action of estrogen at the level of the dopami ne transporter. (C) 2001 Elsevier Science Inc.