Effects of Postnatal Trimethyltin or Triethyltin Treatment on CNS Catecholamine, GABA, and Acetylcholine Systems in the Rat

Abstract

The effects on brain neurochemistry of 2 neurotoxic compounds, trimethyltin (TMT) hydroxide and triethyltin (TET) sulfate, were examined. Long-Evans rats were treated with TMT hydroxide (1 mg/kg, i.p.) on alternate days from day 2-29 of life. These treatments caused a weight deficit of 10-20% by the time the animals were killed on day 55 by head-focused microwave irradiation. These TMT treatments caused severe neuronal loss in the hippocampus and lesser damage in other brain regions. The concentration of GABA was decreased in the hippocampus; acetylcholine and choline concentrations were unaffected. TMT-induced effects on GABA systems were greater than that due simply to generalized neuronal loss. The TMT treatments also caused a significant decrease in dopamine concentrations in the striatum, but did not alter the concentrations of dihydroxyphenylacetic acid or homovanillic acid, the acidic metabolites of dopamine. Concentrations of dopamine and norepinephrine in the brain stem and norepinephrine in the cerebellum were not altered. Despite reports in the literature of TMT-induced neuronal damage in areas of the cortex, no effects on GABA, acetylcholine or choline levels were found in the cortical areas examined, or in the hypothalamus. TET sulfate (0.3 mg/kg per day) was administered for 6 consecutive days of every week during days 2-29 of life. This dose was lower than that needed to cause intramyelin edema, yet it resulted in long-term behavioral changes. No changes in the concentration of any measured neurotransmitter or metabolite were detected. Neurochemical methods should not be used as neurological screens, but rather to define specific mechanisms suggested by detailed behavior, pharmacological and/or physiological studies.