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 a nd McMillan, 1986; Bushnell and Angell, 1992). The monoamine (MA) neur ons are known to be sensitive to TMT, however, a detailed temporal des cription 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, wh ereas the levels of dopamine were unaltered. In addition, a reduced de nsity of 5-HT immunoreactive fibers was seen in hippocampus and cortex . The lesion in the serotonergic and noradrenergic systems was followe d by a recovery. Twelve weeks after TMT treatment, 5-HT and NA levels were increased in hippocampus, and 5-HT levels in striatum. In cerebel lum, NA, 5-HT and 5-HIAA levels were decreased at 12 weeks. Compensato ry processes led to recovered levels of 5-HT and NA in all regions but cerebellum, although regionally specific increases developed with tim e possibly due to hyperinnervation. Inhibition of the aromatic amino a cid decarboxylase with NSD1015 yields accumulation of catecholamine an d 5-HT precursors. Two weeks after TMT, levels of 5-HTP and L-dopa wer e not different in the TMT-treated rats as compared to controls, indic ating that TMT does not affect MA synthesis. (C) 1995 Intox Press, Inc .