Acute effects of pyrethroids on serotonin release in the striatum of awake rats: an in vivo microdialysis study.

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.