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Effects of the Antipsychotic Drug, Haloperidol, on Reproduction in the Fathead Minnow
MAKYNEN, E. A., E. J. DURHAN, M. D. KAHL, K. M. JENSEN, D. L. VILLENEUVE, D. MARTINOVIC, AND G. T. ANKLEY. Effects of the Antipsychotic Drug, Haloperidol, on Reproduction in the Fathead Minnow. Presented at SETAC Annual Meeting, Tampa, FL, November 16 - 20, 2008.
The purpose of these studies was to investigate whether exposure to dopamine receptor antagonists, like haloperidol would adversely impact fish reproduction through modulation of the HPG axis.
Haloperidol is a butyrophenone antipsychotic drug used for the treatment of human hyperactive and manic disorders, agitation, and schizophrenia. The drug is thought to act through antagonism of dopaminergic receptors. We have studied a variety of endocrine-disrupting chemicals with the ability to disrupt steroidogenesis and reproduction through interaction with the hypothalamic-pituitary-gonadal (HPG) axis primarily as agonists or antagonists of the estrogen and androgen receptors or through effects on aromatase activity. The purpose of these studies was to investigate whether exposure to dopamine receptor antagonists, like haloperidol would adversely impact fish reproduction through modulation of the HPG axis. Adult fathead minnows were exposed to haloperidol (0, 0.2, 2.0, and 20 ìg/L) for 21 d in a flow-through system. Endpoints assessed included survival, fish behavior, fecundity, appearance, plasma vitellogenin and steroid concentrations, gonad histopathology, and gene expression. With the exception of a significant increase in gonadotropin releasing hormone (GnRH) transcripts in the brains of males exposed to 20 ìg/L, haloperidol had no significant effects on fathead minnow reproductive success or HPG axis endpoints. Microarray analysis of mRNA transcripts expressed in the ovary tissue of fathead minnows exposed to haloperidol for 96 h suggested impacts on the expression of genes related to selenium binding, steroid receptor-activity, endocrine system development and metallopeptidase activity. However, short-term transcriptional changes were not linked to longer term adverse outcomes. Overall, our testing did not support the hypothesis that dopaminergic antagonists like haloperidol would disrupt fathead minnow reproduction.