Antagonism by d-amphetamine of trimethyltin-induced hyperactivity evidence toward an animal model of hyperkinetic...

In male rats of the Long-Evans strain, either 7.0 mg/kg of trimethyltin (TMT) or 0.9% NaCl was administered by intragastric gavage. After a period of recovery from the typical signs of trimethyltin toxicity, each rat was tested at 72-hr intervals for its locomotor activity in an open field apparatus, the floor of which was divided into square grids. The baseline activity of each of the trimethyltin-treated rats was significantly greater than the saline-treated controls. d-Amphetamine, injected intraperitoneally in a dose of 0.5 or 2.0 mg/kg, augmented the hyperactivity of the trimethyltin-treated animals. However, a 4.0 mg/kg dose of d-amphetamine markedly attenuated the hyperactivity of trimethyltin-treated rats while elevating that of the controls. Since trimethyltin produced an autism-like behavioral disorder involving hyperactivity, preservation, aggressiveness and impairment in problem-solving and memory function, the placating effect of amphetamine supports the proposition that the pathology due to trimethyltin may represent an experimental analogue to the hyperkinetic syndrome in children.