NEUROLEPTICS AND DOPAMINE TRANSPORTERS

The effects of neuroleptic treatments on dopamine transporters and on dopamine receptors was investigated in the forebrain of adult rats tre ated for 21 days with either haloperidol, clozapine or saline. The dop amine D-1 receptors, labeled with [H-3]SCH23390, increased in nucleus accumbens, latero-dorsal rostral neostriatum and substantia nigra, aft er clozapine but not haloperidol. The dopamine D-2 receptors, studied with [SH]raclopride, increased in nucleus accumbens and in dorsolatera l, ventro-medial and dorso-medial quadrants of the rostral neostriatum after either haloperidol or clozapine treatments, and also in latero- ventral rostral neostriatum but only after haloperidol. Haloperidol al so up-regulated D-2 receptors in rostral and caudal neostriatum, but c lozapine produced a more uneven increase, especially in caudal neostri atum. In contrast, the densities of dopamine uptake sites, or transpor ters, labeled with [I-125]RTI-121, remained unchanged after both neuro leptic treatments. The observation that dopamine transporters are resi stant to treatments that modify D-1 and D-2 receptors indicates that t hese uptake sites can probably be ruled out as the target of neurolept ic drugs, and that dopamine receptor up-regulations can indeed occur i ndependently of the densities of nerve endings at the terminal fields of innervation.