Time-course of trimethyltin effects on the monoaminergic systems of the rat brain

The normalization of certain behavioral functions after a trimethyltin (TMT) insult indicates that compensatory processes may occur (Paule and McMillan, 1986; Bushnell and Angell, 1992). The monoamine (MA) neurons are known to be sensitive to TMT, however, a detailed temporal description of the effects is lacking. One week after TMT exposure, 8 mg/kg i.p. to adult male Sprague-Dawley rats, the levels of serotonin (5-HT) and noradrenaline (NA) were decreased in several brain regions, whereas the levels of dopamine were unaltered. In addition, a reduced density of 5-HT immunoreactive fibers was seen in hippocampus and cortex. The lesion in the serotonergic and noradrenergic systems was followed by a recovery. Twelve weeks after TMT treatment, 5-HT and NA levels were increased in hippocampus, and 5-HT levels in striatum. In cerebellum, NA, 5-HT and 5-HIAA levels were decreased at 12 weeks. Compensatory processes led to recovered levels of 5-HT and NA in all regions but cerebellum, although regionally specific increases developed with time possibly due to hyperinnervation. Inhibition of the aromatic amino acid decarboxylase with NSD1015 yields accumulation of catecholamine and 5-HT precursors. Two weeks after TMT, levels of 5-HTP and L-dopa were not different in the TMT-treated rats as compared to controls, indicating that TMT does not affect MA synthesis.