Clothianidin (CLO) is a neonicotinoid insecticide that produces toxic effects in experimental animals and humans. These effects are associated primarily to its action as a nicotinic agonist, acting on insect and vertebrate nicotinic acetylcholine receptors (nAChRs), but little is known about the mechanisms of action on the mammalian nervous system. In the rat striatum, CLO induces increases in the dopamine overflow in a concentration-dependent manner. In the present study, we evaluate, using in vivo brain microdialysis in adult Sprague-Dawley rats, the participation of specific nAChRs and muscarinic cholinergic receptors (mAChRs) on CLO-induced striatal dopamine release. We investigate the effects of selective antagonists of α4β2 heteromeric, β2 subunit, α7 nAChRs, and of broad-spectrum antagonist of mAChRs (atropine) on CLO-induced dopamine release. Intrastriatal administration of antagonists of α4β2 N-n-decilonicotinium iodide (NDNI), and of α7 methylcaconitine (MLA) significantly decreased the CLO-induced dopamine overflow in a concentration-dependent form, whereas pretreatment with the antagonist of β2 subunit DHβE not having effect. Pretreatment with the muscarinic antagonist atropine also blocked the increases in the extracellular dopamine levels. Taken together, these results suggest that the stimulatory effect of CLO on in vivo dopamine from rat striatum depends on the activation of α4β2 present in dopaminergic terminals and α7 nAChRs subtypes expressed in glutamatergic terminals in the striatum. On the other hand, the CLO-induced dopamine release also appears to involve the activation of mAChRs.
Keywords: Acetylcholine receptors; Cerebral microdialysis; Clothianidin; Dopamine; Neonicotinoids pesticides; striatum.
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