Abstract
The aim of this thesis was to develop a method to study the effects of toluene in the central nervous system of the rat. Microdialysis on awake rats was used to study toluene's effects on the transmission of dopamine, acetylcholine, glutamate and aspartate in the striatum, and on GABA in the striatum, the cerebellum and the globus pallidus. A comparison between toluene's and halothane's effects on GABA neurotransmission in the cerebellum was also made. By recording eye movements, the acute 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 inhalation exposure, while levels of the dopamine metabolite HVA remained constant. The fact that HVA levels were not affected indicates that toluene blocks dopamine reuptake. Acute toluene exposure did not notably affect glutamate or aspartate transmission in the striatum. Acetylcholine release in the striatum decreased during and after acute toluene exposure. In contrast, elevating extracellular dopamine by the use of a dopamine uptake blocker increased acetylcholine release. Toluene exposure immediately before tail pinch, which is known to increase dopamine release, did not change the acetylcholine response to tail pinch. Thus, the decrease in acetylcholine release due to toluene exposure is probably not mediated through dopamine neurotransmission.
Extracellular GABA levels in the striatum remained stable, while GABA in the globus pallidus decreased during exposure. In contrast, extracellular GABA in the cerebellum increased during toluene exposure. Thus, toluene has regional specific effects on GABA transmission in the central nervous system. Halothane caused no noticeable effect 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 of tolune's effect on the vestibulo-oculomotor reflex, confirm the hypothesis that toluene affects the vestibulo-oculomotor reflex via a change in GABA neurotransmission. Toluene had regional specific effects as well as transmitter specific effects on brain neurotransmission. Toluene caused either decrease in neurotransmitter release (acetylcholine) or increase in extracellular level (dopamine), and toluene's effect on GABA differed in all three regions studied. Thus, it appears that toluene has no "general effect" upon brain neurotransmission.
