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Keywords:

  • Pyrethroids;
  • Microdialysis;
  • Striatum;
  • Serotonin;
  • Tetrodotoxin;
  • Nimodipine

ABSTRACT

The present study examined the acute neurotoxic effects of three different pyrethroids, allethrin, cyhalothrin, and deltamethrin on the release of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the striatum of conscious rats using microdialysis. Allethrin 10 mg/kg reduced extracellular levels of 5-HT to 46%, whereas 20 and 60 mg/kg increased the release to 177% and 243% of baseline, respectively. Cyhalothrin increased 5-HT release to 145–204% and deltamethrin decreased to 58–32% of baseline in a dose-dependent manner. None of the pyrethroids tested altered extracellular levels of 5-HIAA. Local infusion of the voltage-gated sodium channel antagonist tetrodotoxin (TTX) into striatum completely prevented the effects of allethrin, cyhalothrin, and deltamethrin (10 and 20 mg/kg) on 5-HT release. The effect of deltamethrin at 60 mg/kg was completely abolished by striatal infusion of nimodipine (L-type Ca++ channel antagonist) with TTX. These findings suggest that pyrethroids disrupt the serotonergic neurotransmission in striatum in a dose-related manner with Na+ and Ca2+ channel-dependent mechanisms. © 2012 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:150-156, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.21450