Temporal changes in dopaminergic and serotonergic function caused by administration of trimethyltin to adult rats

Previous studies have demonstrated that at day 7 following treatment, administration of 3 or 7 mg/kg trimethyltin (TMT) to male Long-Evans rats caused decreases in the concentrations of DA in nucleus accumbens, and perturbed serotonergic function in regions of brain that receive serotonergic innervation from the raphe nuclei. The present series of experiments extended these observations by examining the time course of these events from 14 to 28 days after treatment. Following a dose of 7 mg/kg, changes in serotonergic function, as evidenced by increased turnover and decreased concentrations of 5-HT, were present in striatum, olfactory tubercle, septum and frontal cortex. In nucleus accumbens, concentrations of DA were decreased up to 21 days, while in frontal cortex concentrations of DOPAC and HVA were elevated only at 14 days. In concert with our previous studies, these data indicate that administration of TMT continues to affect serotonergic systems up to 28 days, and dopaminergic systems up to 21 days after exposure, with striatum, nucleus accumbens, olfactory tubercle and septum exhibiting persistent effects due to administration of this neurotoxicant. These prolonged alterations in serotonergic function suggest that this system may play an important role in the response to intoxication with TMT.