[3H] citalopram binding to serotonin transporter sites in minnow brains

Georgianna G. Gould, Bryan W. Brooks, Alan Frazer

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Mammalian serotonin (SERT) and norepinephrine transporters (NET) are target sites for antidepressants and are affected by pesticide exposures. Herein, we examined whether golden shiner (Notemigonus crysoleucas) or fathead minnow (Pimphales promelas) SERTs and catecholamine transporters respond comparably to mammalian SERTs and NETs. We compared the pharmacological profiles of central SERT and NET binding sites of the golden shiner minnow to those of rats. Homogenate binding with the radioligand [3H] citalopram indicated that golden shiner SERT has a KD of 7 ± 3 nM and a B max of 226 ± 46 fmol/mg protein. These values are similar to those of rat cortical SERT (KD 1.4 ± 0.1 nM and B max 240 ± 48 fmol/mg protein). We also examined SERT binding in fathead minnow brain, and found it similar to that of the golden shiner. A putative golden shiner NET, measured using [3H] nisoxetine, had KD = 12 ± 5 nM and Bmax = 187 ± 49 fmol/mg protein, whereas rat hippocampal NET had KD = 5 ± 2 nM and Bmax = 93 ± 8 fmol/mg protein. Minnow SERT and NET binding is displaceable by selective reuptake inhibitors. Finally, we exposed zebrafish (Danio rerio) to the serotonin reuptake inhibiting antidepressant sertraline or the organophosphate chlorpyrifos for 21 days. After either treatment, SERT binding was reduced by 50% (n = 3-6, P < 0.05). In summary, minnow central SERT and NET express slightly lower affinity for antidepressants than rats. However, magnitudes of affinity are similar, and minnow SERT binding is decreased by chronic sertraline or chlorpyrifos administration.

Original languageEnglish (US)
Pages (from-to)203-210
Number of pages8
JournalBasic and Clinical Pharmacology and Toxicology
Volume101
Issue number3
DOIs
StatePublished - Sep 1 2007

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ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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