Abstract

The neurotoxic pyrethroid, deltamethrin, induces a severe motor syndrome characterised by tremor and choreoathetosis when injected systemically to rats. The interaction between deltamethrin and the two major dopaminergic pathways - the nigrostriatal and mesolimbic pathways - was investigated in rats. Striatal catecholamines, indoleamines and metabolites were measured by HPLC with electrochemical detection. Unilateral injection of deltamethrin (1.0 microgram) into the ventral tegmental nucleus or substantia nigra induced rapid ipsilateral or contralateral circling respectively but was ineffective at other basal ganglia sites. Both the sham and vehicle injections at either site, resulted in a marked increase above normal in DA turnover in the ipsilateral striatum without inducing circling behaviour. DA turnover was increased to the same extent in the ipsilateral stratum of deltamethrin-treated rats where rapid circling was present. Therefore the neurochemical findings were not consistent with the rotation theories based on striatal DA asymmetry but rather followed alternative mechanisms previously proposed, where circling behaviour can occur by mechanisms not causally related to striatal DA. These findings also indicate that a degree of selectivity exists in the action of deltamethrin, a sodium channel toxin that might be expected to act on all neuronal systems within the SN or VTN or equally at other sites within the basal ganglia associated with circling behaviour.

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