Alterations in serotonin transporter expression in brain regions of rats exposed neonatally to chlorpyrifos

Chlorpyrifos (CPF), one of the most widely-used organophosphate pesticides, is a suspected neuroteratogen. We administered CPF to neonatal rats on pos tnatal days (PN) 1-4 (1 mg/kg) or PN11-14 (5 mg/kg), treatments devoid of o vert toxicity. At the end of the treatment period (PN5 and 15, respectively ) and 5-7 days later, we then examined the effects on paroxetine (PXT) bind ing to the presynaptic 5HT high-affinity transporter, a marker for serotoni n (5HT) projections. In males, we found a persistent decrease in PXT bindin g across the two different treatment regimens, with deficits apparent in a brain region containing 5HT terminal fields (forebrain) as well as in a re- ion containing 5HT cell bodies (brainstem). In contrast, females given the early treatment regimen (PN1-4) showed deficits in the brainstem but transi ent elevations in the forebrain; the later treatment regimen (PN11-14) had no significant effect on PXT binding in females. These data are consistent with earlier work showing brainstem cell injury resulting from neonatal CPF exposure, and indicate specific damage to 5HT neurons, with a consequent l oss of transporter expression in both terminal fields and perikarya. In fem ales, the damage may be temporarily offset by initial trophic effects in th e terminal region, consequent to the cholinergic stimulation evoked by chol inesterase inhibition via the active metabolite, CPF oxon. The gender-selec tive effects on 5HT systems are likely to contribute to similar gender dimo rphism in behavioral performance. Because the CPF effects involve 5HT, a ne urotransmitter intimately involved in the control of mood, we suggest the n eed to evaluate behaviors that typify animal models of depression. (C) 2001 Elsevier Science B.V. All rights reserved.