| Alterations in Central Nervous System Serotonergic and Dopaminergic Synaptic Activity in Adulthood after Prenatal or Neonatal Chlorpyrifos Exposure Justin E. Aldridge,1 Armando Meyer,1,2 Frederic
J. Seidler,1 and Theodore A. Slotkin1 1Department of Pharmacology and Cancer Biology, Duke University
Medical Center, Durham, North Carolina, USA; 2Centro de Estudos
da Saúde do Trabalhador e Ecologia Humana, Escola Nacional de Saúde
Pública, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil Abstract
Exposure to chlorpyrifos (CPF) alters neuronal development of serotonin (5HT) and dopamine systems, and we recently found long-term alterations in behaviors related to 5HT function. To characterize the synaptic mechanisms underlying these effects, we exposed developing rats to CPF regimens below the threshold for systemic toxicity, in three treatment windows: gestational days (GD) 17-20, postnatal days (PN) 1-4, or PN11-14. In early adulthood (PN60) , we assessed basal neurotransmitter content and synaptic activity (turnover) in brain regions containing the major 5HT and dopamine projections. CPF exposure on GD17-20 or PN1-4 evoked long-term increases in 5HT turnover across multiple regions ; the effects were not secondary to changes in neurotransmitter content, which was unaffected or even decreased. When the treatment window was shifted to PN11-14, there were no long-term effects. Dopamine turnover also showed significant increases after CPF exposure on GD17-20, but only when the dose was raised above the threshold for overt toxicity ; however, hippocampal dopamine content was profoundly subnormal after exposures below or above the acute, toxic threshold, suggesting outright neurotoxicity. These results indicate that, in a critical developmental period, apparently nontoxic exposures to CPF produce lasting activation of 5HT systems in association with 5HT-associated behavioral anomalies. Key words: brain development, chlorpyrifos, dopamine, organophosphate pesticides, serotonin. Environ Health Perspect 113: 1027-1031 (2005) . doi:10.1289/ehp.7968 available via http://dx.doi.org/ [Online 28 April 2005]
Address correspondence to T.A. Slotkin, Box 3813 DUMC, Duke University Medical Center, Durham, NC 27710 USA. Telephone: (919) 681-8015. Fax: (919) 684-8197. E-mail: t.slotkin@duke.edu This work was supported by National Institutes of Health grants ES10387, ES10356, and ES07031. The authors declare they have no competing financial interests. Received 27 January 2005 ; accepted 28 April 2005. The full version of this article is available for free in HTML or PDF formats. |
