Effects of trimethyltin on hippocampal dopaminergic markers and cognitive behaviour.

The triorganotin compound trimethyltin (TMT) is a highly toxic molecule which has a great impact on human health. The aim of this study was to investigate the specific alteration of dopamine receptors and transporters in the hippocampus of TMT-treated rats. The TMT-treated group showed impaired spatial reference memory in a Morris water maze task compared to the control group, whereas memory consolidation tested 24 hours after the last training session was preserved. In the open field, TMT-treated rats showed a decrease in time spent in rearing episodes reflecting a lower interest to explore a novel environment. In the hippocampal area of the TMT-treated group, we observed a reduction in neuronal viability accompanied by a significant decrease in the expression of the dopamine receptors (D1 and D2), and dopamine transporters (DAT, VMAT1 and VMAT2). A less pronounced reduction was observed for D3 and D5 while D4 did not change. These data were confirmed by RT-PCR analysis. The present study on TMT-induced neurodegeneration highlights the link between hippocampal asset of dopamine receptors and transporters and the impaired performance of rats in a spatial reference memory task.