Received for publication June 6, 2008.
Revised July 2, 2008.
Accepted for publication July 3, 2008.

Paraquat exposure reduces nicotinic receptor-evoked dopamine release in monkey striatum

Abstract

Paraquat, an herbicide widely used in the agricultural industry, has been associated with lung, liver, and kidney toxicity in humans. In addition, it is linked to an increased risk of Parkinson's disease. For this reason, we had previously investigated the effects of paraquat in mice and showed that it influenced striatal nicotinic receptor (nAChR) expression but not nAChR-mediated dopaminergic function. Since non-human primates are evolutionarily closer to humans and may better model the effects of pesticide exposure in man, we examined the effects of paraquat on striatal nAChR function and expression in monkeys. Monkeys were administered saline or paraquat once weekly for six weeks, after which nAChR levels and receptor-evoked ³H-dopamine (³H-DA) release were measured in striatum. The functional studies showed that paraquat exposure attenuated dopamine (DA) release evoked by 3/62* nAChRs, a subtype present only on striatal dopaminergic terminals, with no decline in release mediated by 42* nAChRs, present on both DA terminals and striatal neurons. Paraquat treatment decreased 42* but not 3/62* nAChR expression. The differential effects of paraquat on nAChR expression and receptor-evoked ³H-DA release emphasize the importance of evaluating changes in functional measures. The finding that paraquat treatment has a negative impact on striatal nAChR-mediated dopaminergic activity in monkeys but not mice indicates the need for determining the effects of pesticides in higher species.

Key words: Parkinson's disease, alpha6, conotoxin, environmental toxin, nicotine, nigrostriatal damage