Parallel changes in operant behavioral adaptation and hippocampal corticosterone binding in rats treated with trimethyltin.

Rats were given water vehicle or trimethyltin (TMT; 3.0, 6.0 or 7.5 mg/kg, p.o.). Lever responding for food was measured 3 months later, in a test in which the fixed ratio requirement was doubled daily (FR1-128). Response rates for all groups were inverted U-shaped functions of FR values. However, the effect of increasing ratio values was attenuated in the 6.0 mg/kg group, which responded less than controls when control rates were maximal (at FR16 and FR32). In contrast, rats given the high dose responded at higher rates (at FR4 and FR64). [3H]Corticosterone binding to hippocampal cytosolic protein was maximally reduced for the group given 6.0 mg TMT/kg. The greatest reduction in hippocampal weight resulted from injection of 7.5 mg TMT/kg, but a smaller reduction in [3H]corticosterone binding (i.e. 22%) was observed for this group. In the absence of an effect of 3.0 mg TMT/kg upon weight of hippocampus, there also was a reduction in steroid binding, indicating the sensitivity of this parameter for TMT toxicity. The results support the notion that hippocampal corticosteroid receptors are important for behavioral adaptation, and rats given moderate doses of TMT may be useful for studying functions of corticosterone receptors.