Effects of triethyltin on responding of mice under a multiple schedule of reinforcement

The lethality and behavioral effects of triethyltin (TET) were determined in adult, male BALB/c mice. Following a single IP dose of TET (10, 12.5 or 15 mg/kg), the lethality was determined at 24-hr intervals. By 144 hr after TET administration, lethality had risen to greater than 90% in the groups receiving the 12.5 and 15 mg/kg and 20% (6/30) in the group which received 10 mg/kg. No additional deaths were observed over the remainder of the two week observation period. The behavioral effects of 5, 7.5 or 10 mg/kg were determined in mice trained to respond under a multiple fixed-ratio 30, fixed-interval 600-sec schedule of milk presentation. At 3 hr after TET administration, the rate of responding was decreased at all three doses. However, by 27 hr after 5 or 7.5 mg/kg TET the rate of responding had returned to pre-injection control values while the responding of the mice in the 10 mg/kg group did not return to pre-injection control values until 51 hr after administration. In a separate group of mice, 7.5 mg/kg was administered at 2 week intervals for a total of 5 separate administrations. No evidence for a cumulative or diminished behavioral effect was observed. Neuropathological examination revealed a direct dose and time related pathology in the white matter of the CNS. Maximal edematous vacuolar change was observed 72 hr after TET administration. Such morphological changes, however, were totally absent 12 days after a single 10 mg/kg exposure. Multiple exposure to TET (7.5 mg/kg) at 2 week intervals for 10 weeks showed only minimal morphological alterations in the brain.