Chronic subanesthetic halothane exposure causes selective alterations in neurotransmitter systems in discrete brain regions

Abstract

The effects of prolonged exposure to subanesthetic concentrations of halothane on dopaminergic, noradrenergic, cholinergic, and GABAergic neuronal systems were studied in discrete regions of the rat brain. Exposures to 0.25% halothane in air were for 8 h/day, 5 days/week during an 8-week period; control rats received only air at an equivalent flow rate. Twenty-four hours after the last exposure the animals were killed and brain, liver, muscle, and serum samples were taken for analyses. Discrete brain regions were removed by microdissection and assayed for norepinephrine, dopamine, glutamate decarboxylase, choline acetyltransferase, and proteins. The remaining tissues and serum were analyzed for halothane content; however, halothane was not detected in any sample tested. Rats which were exposed to halothane exhibited a marked reduction in body weight gain and their urine volume was significantly greater than in the controls. Significant changes were observed in regions associated with the limbic system, for example, dopamine was increased in the ventral tegmental area, choline acetyltransferase was increased in the nucleus accumbens, caudate, and globus pallidus and its activity decreased in the central gray. The activity of glutamate decarboxylase was decreased in the accumbens and in the medial preoptic nuclei but increased in the lateral preoptic nucleus. There was no apparent effect on norepinephrine concentrations. We suggest that these selective changes in limbic regions may cause behavioral deficits consequent to chronic subanesthetic halothane exposure.