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

Abstract

The effect of cocaine exposure during the preweaning period on the function of the central dopaminergic systems was determined in adult rats. The present 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 kg(-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 [3H]R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-b enzazepine ([3H]SCH 23390) for the dopamine D1 receptor and [3H]raclopride for the dopamine D2 receptor was carried out. The results show that haloperidol increased [3H]raclopride binding in many forebrain regions. Preweaning cocaine treatment in males increased the area showing this effect. Males generally were more responsive to haloperidol than females. However, in GBR 12909-treated females, raclopride binding showed widespread increases following haloperidol injection. For SCH 23390 binding, most regions showed a significant interaction between haloperidol, sex and preweaning treatment group. This was due primarily to the GBR 12909-treated males, which showed elevated basal dopamine D1 receptor binding levels and a haloperidol-induced reduction in dopamine D1 receptor binding in most regions evaluated. 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 effects than cocaine on both raclopride and SCH 23390 binding following chronic haloperidol injection.