Developmental exposure to methylmercury alters behavioral sensitivity to d-amphetamine and pentobarbital in adult rats

Female rats were exposed to 0, 0.5, or 6.4 ppm methylmercury in their drink ing water before mating, and throughout gestation and lactation. When the f emale offspring were 4-6 months old, they were trained to respond under a m ultiple differential reinforcement of high rate (DRH) 9:4 - Extinction sche dule of reinforcement. No differences among exposure groups were apparent i n steady-state behavior. Drug challenges were conducted with multiple doses of d-amphetamine, scopolamine, pentobarbital, haloperidol, and dizocilpine , drugs selected for their different pharmacological effects. The ED50 valu es for amphetamine's reinforcement rate-reducing effects for the control, 0 .5-, and 6.4-ppm groups were 3.1, 1.9, and 0.9 mg amphetamine/kg body weigh t, respectively, demonstrating an increased sensitivity to d-amphetamine in methylmercury-exposed rats. Rats in the 6.4-ppm group also demonstrated a relative insensitivity to pentobarbital. Further, these exposed rats exhibi ted an inverted U-shaped dose-effect curve under the pentobarbital dose-eff ect -determination, while controls showed only a declining curve. Exposed r ats did not respond differentially to haloperidol, scopolamine, or dizocilp ine, suggesting specificity. The present data suggest an involvement of cat echolaminergic and GABAergic activity in methylmercury's neurotoxicity. (C) 2001 Elsevier Science Inc. All rights reserved.