Acute Effects of Pyrethroids on Serotonin Release in the Striatum of Awake Rats: An In Vivo Microdialysis Study

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.

Pyrethroid Insecticides Directly Activate Microglia Through Interaction With Voltage-Gated Sodium Channels

“…Indeed, we previously found that the rise in Ca 2þ influx into the SK-N-AS is secondary to the activation of Na þ channels following exposure to deltamethrin (Hossain and Richardson, 2011). Evidence from our microdialysis studies also demonstrate that the inhibition of L-type calcium channel can prevent the Na þ channel-independent effects of pyrethroids on release of extracellular neurotransmitters in rat (Hossain et al, 2013b;Hossain et al, 2006Hossain et al, , 2008. Similarly, Cao et al (2011) showed that deltamethrin potently stimulates calcium influx in cortical neurons and that secondary calcium influx may be mediated by L-type calcium channels or reversal of the Na þ / Ca 2þ exchanger.…”

Deltamethrin Exposure Daily From Postnatal Day 3–20 in Sprague-Dawley Rats Causes Long-term Cognitive and Behavioral Deficits

“…Data analyses. Some developmental effects of DLM were reported previously (Hossain et al, 2013(Hossain et al, , 2015Richardson et al, 2015), therefore, we hypothesized deficits for these outcomes. These data were analyzed using a priori methods.…”

“…In addition to alterations in DA biomarkers, Richardson et al (2015) observed deficits in learning, memory, attention, and impulsivity, and increased open-field (OF) activity. By contrast, in adult rats, DLM alters serotonin as well as DA (Hossain et al, 2006(Hossain et al, , 2013. Gestational DLM exposure in rats causes deficits in learning and memory (L&M) when tested at 6-12 weeks of age, alters cholinergic circuitry, increases striatal 3, 4-dihydroxyphenylacetic acid (DOPAC) levels, alters OF activity and rearing, and reduces cytochrome P450s (Aziz et al, 2001;Johri et al, 2006;Lazarini et al, 2001).…”

Evaluation of changes in monoamine levels and apoptosis induced by cyfluthrin in rats

“…19 The administration of cyhalothrin to rats at the dose levels of 10, 20 and 60 mg kg −1 caused dose-dependent increases of striatal 5-HT, but no changes were seen in the outflow of 5-HIAA. 20 In a study aimed at determining the effect of permethrin on striatum, median prefrontal cortex and hippocampal monoamine levels, a statistically insignificant increase in 5-HT levels was found in the study group treated with 34 mg kg −1 permethrin, whereas the 5-HIAA levels remained unchanged. 21 There are some studies showing both no change and a decrease in the 5-HT and 5-HIAA levels in the brain following pyrethroid administration.…”