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 function. Recent reports indicate that heptachlor exposure also alters dopamine transporter (DAT) expression and function in adult mice. The aim of this study was to determine whether gestational, perinatal, and/or adolescent heptachlor exposure in rats altered dopamine-receptor and DAT binding. Adolescent exposure to dieldrin was included to evaluate the generality of the findings. 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 > or =3 mg/kg/day. There were no changes in striatal dopamine receptor-D1 ([(3)H]SCH-23390) and -D2 ([(3)H]spiperone) binding in preweanling pups exposed perinatally to heptachlor, and no differences in the response of adult rats to the motor activity-increasing effects of d-amphetamine. However, there were significant (27-64%) increases in striatal DAT binding of [(3)H]mazindol in preweanling rats exposed only gestationally. In rats exposed perinatally and/or during adolescence, there were also increases (34-65%) in striatal DAT binding at postnatal days (PND) 22, 43, and 128. Adolescent exposure to dieldrin also increased DAT binding. In other rats exposed perinatally 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 indicated that heptachlor (> or =10 microM) displaced mazindol binding. Thus, gestational, perinatal, and/or adolescent exposure to heptachlor produced an increase in DAT binding as early as PND 10, and this change persisted into adulthood.
Purkerson-Parker
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The University of North Carolina, Curriculum in Toxicology, Chapel Hill, NC 27599, USA.
McDaniel
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KL
Moser
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VC
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D004305:Dose-Response Relationship, Drug; D005260:Female; D006533:Heptachlor / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins; D011247:Pregnancy; D011485:Protein Binding / Q000187:drug effects; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; D007306:Insecticides; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C493216:Slc6a3 protein, rat; D006533:Heptachlor