Dopamine transporter binding in the rat striatum is increased by gestational, perinatal, and adolescent exposure to heptachlor

Heptachlor is a persistent cyclodiene pesticide that affects GABAergic func tion. Recent reports indicate that heptachlor exposure also alters dopamine transporter (DAT) expression and function in adult mice. The aim of this s tudy was to determine whether gestational, perinatal, and/or adolescent hep tachlor exposure in rats altered dopamine-receptor and DAT binding. Adolesc ent exposure to dieldrin was included to evaluate the generality of the fin dings. Sprague-Dawley rats received doses (po) ranging from 0 to 8.4 mg/kg/ day of heptachlor, or dieldrin, 3 mg/kg/day, during different developmental periods. There were dose-related decreases in maternal weight gain and pup survival, as well as delayed righting reflex, at heptachlor doses greater than or equal to3 mg/kg/day. There were no changes in striatal dopamine rec eptor-D1 ([H-3]SCH-23390) and -D2 ([H-3]spiperone) binding in preweanling p ups exposed perinatally to heptachlor, and no differences in the response o f adult rats to the motor activity-increasing effects of d-amphetamine. How ever, there were significant (27-64%) increases in striatal DAT binding of [H-3]mazindol in preweanling rats exposed only gestationally. In rats expos ed perinatally and/or during adolescence, there were also increases (34-65% ) in striatal DAT binding at postnatal days (PND) 22, 43, and 128. Adolesce nt exposure to dieldrin also increased DAT binding. In other rats exposed p erinatally and throughout adolescence, even the lowest dose of heptachlor 0 .3 mg/kg/d increased DAT binding on PND 130. The DAT affinity for mazindol was unchanged in heptachlor-exposed striata. In vitro binding studies indic ated that heptachlor (greater than or equal to 10 muM) displaced mazindol b inding. Thus, gestational, perinatal, and/or adolescent exposure to heptach lor produced an increase in DAT binding as early as PND 10, and this change persisted into adulthood.