Brain microdialysis study of the effects of hazardous chemicals on the central nervous system. 1. Changes in monoamine metabolites induced by cerebral methyl bromide administration measured by two-probe microdialysis (TPMD) method.

The two-probe microdialysis (TPMD) method, in which two probes were applied simultaneously to the rat head, was developed to directly investigate the effects of chemicals on the brain. The first and the second probes were implanted into the right striatum and the left ventricle, respectively. Chemicals were dissolved in the perfusion fluid and given into the brain by diffusion through the ventricle probe. Monoamine metabolites were recovered through the striatum probe to investigate changes in neurotransmitter substances. Both intraperitoneal and intraventricular administration of haloperidol (a dopamine receptor blocker) increased 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA, dopamine metabolites) concentrations in the striatum. On the other hand, apomorphine (a dopamine receptor stimulant), which was given both intraperitoneally and intraventricularly, decreased striatal DOPAC and HVA concentrations. 5-Hydroxyindoleacetic acid (5HIAA, a serotonin metabolite) concentration was not affected by these drugs. Regarding changes in monoamine neurotransmitters, systemic and intraventricular administration produced similar effects. These findings indicate that the drugs were effectively incorporated into the brain by the TPMD method and the drug effect was observed in the opposite brain hemisphere. In the same procedure as used in the administration of haloperidol and apomorphine, methyl bromide was given into the rat brain. DOPAC and HVA in the striatum were increased by methyl bromide given by the TPMD method. These changes were the same as observed in the homogenate of rat brain exposed to methyl bromide. 5HIAA was reduced by intraventricular administration by the TPMD method, and this change in 5HIAA was not observed in the exposure experiments. We could detect the direct effects of methyl bromide on the brain by the TPMD method.