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Effects of Dopamine Challenges on Clocked Fixed-Interval Schedule Performance for Rats Prenatally Exposed to Methylmercury and Selenium




Reed, Miranda

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Fish consumption has been linked with health benefits, but fish are also a source of methylmercury (MeHg), a neurotoxicant implicated in well-documented population poisonings. To examine putative MeHg-induced alterations in the function of the dopamine (DA) neurotransmitter system, the offspring of Long-Evans rats were examined. Pregnant rats were exposed to 0, 0.5, or 5 ppm MeHg via their drinking water before mating and during gestation and lactation, as well as to a diet either high or low in selenium (Se), a nutrient hypothesized to protect against MeHg damage, creating 2x3 factorial design. Female offspring of these breeders were weaned at postnatal day 21, at which time exposure to MeHg ended, but special Se diets continued. At eleven months of age, a multiple schedule consisting of alternating fixed interval (FI) and clocked FI (CFI) components was arranged. The CFI component was divided into 5, 24-second bins, each associated with a different auditory stimulus, providing a “clock.” Low and high response rates were evaluated using the initial 40% (bins 1 and 2) and last 20% (bin 5) of the FI and CFI components, respectively. Rats exposed to 5 ppm Hg made more responses than the other two groups during the last 20% of the intervals, regardless of Se exposure or presence of the clock stimuli. They did not differ from the other groups during the initial 40% of the FI and CFI components. Drug challenges were conducted with multiple doses of cocaine, desipramine, SKF-38393, quinpirole, SCH-23390, and sulpiride, drugs selected for their effects on the D1 and D2 receptor subtypes. Animals exposed to 5 ppm MeHg displayed an increased sensitivity to cocaine, whereas the effects of cocaine for the 0.5 ppm Hg groups depended on dietary Se exposure, producing an interaction among cocaine dose, MeHg and Se exposure. There were no other interactions with any of the dopamine direct agonists or antagonists, suggesting that co-activation of the D1 and D2 receptors is required to produce the MeHg interactions seen with cocaine.