Chronic haloperidol alters dopamine receptors: effects of cocaine exposureduring the preweaning period

The effect of cocaine exposure during the preweaning period on the function of the central dopaminergic systems was determined in adult rats. The pres ent study investigated the alterations in dopamine receptors in 93-day-old male and female rats treated with cocaine (50 mg kg(-1) day(-1)), 1-[2-[bis (4-fluorophenyl)methoxyl]-4-[3-phenylpropyl]piperazine (GBR 12909) (50 mg k g(-1) every other day) or water during postnatal days 11-20. Haloperidol (2 mg kg(-1) day) or saline was injected during postnatal days 76-90 and the rats were killed on postnatal day 93. Quantitative receptor autoradiography with [H-3]R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine ([H-3]SCH 23390) for the dopamine D-1 receptor and [H-3]rac lopride for the dopamine D-2 receptor was carried out. The results show tha t haloperidol increased [H-3]raclopride binding in many forebrain regions. Preweaning cocaine treatment in males increased the area showing this effec t. Males generally were more responsive to haloperidol than females. Howeve r, in GBR 12909-treated females, raclopride binding showed widespread incre ases following haloperidol injection. For SCH 23390 binding, most regions s howed a significant interaction between haloperidol, sex and preweaning tre atment group. This was due primarily to the GBR 12909-treated males, which showed elevated basal dopamine D-1 receptor binding levels and a haloperido l-induced reduction in dopamine D-1 receptor binding in most regions evalua ted. These data suggest that inhibition of the dopamine transporter during ontogeny produces long-term alterations in dopamine receptor regulation but that selective inhibitors of the dopamine transporter produced greater eff ects than cocaine on both raclopride and SCH 23390 binding following chroni c haloperidol injection. (C) 1999 Elsevier Science B.V. All rights reserved .