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Acute neuroactive drug exposures alter locomotor activity in larval zebrafish
Citation:
Irons, T. D., R. C. MACPHAIL, D. L. HUNTER, AND S. J. PADILLA. Acute neuroactive drug exposures alter locomotor activity in larval zebrafish. Presented at Society of Toxicology 49th Annual Meeting, Salt Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
acute exposure to MPTP results in changes in locomotor activity that are distinguishable from the effects of developmental exposures.
Description:
In an effort to develop a rapid in vivo screen for EPA's prioritization of toxic chemicals, we are characterizing the locomotor activity of zebrafish (Danio rerio) larvae after exposure to prototypic drugs that act on the central nervous system. MPTP (1-methyl-4phenyl- 1 ,2,3,6-tetrahydropyridine) is a neurotoxicant that destroys dopaminergic neurons, causing parkinsonian siqns in mammals that include abnormalities in locomotor activity. Previous studies with zebrafish in our lab have shown that developmental exposures to MPTP cause a biphasic dose-response pattern in locomotion. Because these results differed from previous findings in both zebrafish and mammals, it was important to identify the dose-response profile of pharmacological effects as well. We hypothesized acute exposure of zebrafish larvae to MPTP would produce locomotor changes separable from those produced by developmental exposures. Zebrafish were raised in a 96-well microtiter plate at 26°C under a 14:10 hr lightdark cycle (lights on at 0730 hr). On the sixth day, the larvae were exposed to 0.8-50 IJM MPTP (n=12/dose/plate, 2 plates). After 20 min, locomotor activity was assessed for 70 min during alternating periods of light and dark (infrared) using video tracking. Acute exposure to MPTP yielded a biphasic dose-response function, with lower doses (0.8 and 1.6 IJM) causing hyperactivity, and higher doses (12.5, 25, and 50 IJM) causing hypoactivity. These results differed from the changes in locomotor activity due to developmental exposures at the same doses, where hyperactivity was seen at intermediate doses (1.6-12.5 IJM) and moderate hypoactivity was seen only at the highest dose (50 IJM). Therefore, acute exposure to MPTP results in changes in locomotor activity that are distinguishable from the effects of developmental exposures.