Acute toluene effects on neurotransmission in the central nervous system

Abstract: The aim of this thesis was to develop a method to study the effects of toluene in thecentral nervous system of the rat. Microdialysis on awake rats was used to studytoluene's effects on the transmission of dopamine, acetylcholine, glutamate andaspartate in the striatum, and on GABA in the striatum, the cerebellum and the globuspallidus. A comparison between toluene's and halothane's effects on GABAneurotransmission in the cerebellum was also made. By recording eye movements, theacute effects of toluene and a selective GABAB antagonist on the vestibulo and opto-oculomotor system in rats were also investigated.Striatal extracellular levels of dopamine increased during acute toluene inhalationexposure, while levels of the dopamine metabolite HVA remained constant. The factthat HVA levels were not affected indicates that toluene blocks dopamine reuptake.Acute toluene exposure did not notably affect glutamate or aspartate transmission inthe striatum.Acetylcholine release in the striatum decreased during and after acute tolueneexposure. In contrast, elevating extracellular dopamine by the use of a dopamineuptake blocker increased acetylcholine release. Toluene exposure immediately beforetailpinch, which is known to increase dopamine release, did not change theacetylcholine response to tailpinch. Thus, the decrease in acetylcholine release due totoluene exposure is probably not mediated through dopamine neurotransmission.Extracellular GABA levels in the striatum remained stable, while GABA in the globuspallidus decreased during exposure. In contrast, extracellular GABA in the cerebellumincreased during toluene exposure. Thus, toluene has regional specific effects onGABA transmission in the central nervous system. Halothane caused no noticeableeffect on GABA in the cerebellum.The result that toluene increases extracellular GABA levels in the cerebellar cortex,and the fact that administration of CGP 35348 (a GABAB antagonist) inhibits some oftolune's effect on the vestibulo- oculomotor reflex, confirm the hypothesis that tolueneaffects the vestibulo- oculomotor reflex via a change in GABA neurotransmission.Toluene had regional specific effects as well as transmitter specific effects on brainneurotransmission. Toluene caused either decrease in neurotransmitter release(acetylcholine) or increase in extracellular level (dopamine), and toluene's effect onGABA differed in all three regions studied. Thus, it appears that toluene has no"general effect" upon brain neurotransmission.key words: acetylcholine, aspartate, cerebellum, dopamine, GABA, globus pallidus,glutamate, microdialysis, rat, striatum, toluene, ISBN 91-628-1938-0 1996 Karl Stengård