Distribution of Inhaled m-Xylene in Rat Brain and its Effect on GABAA Receptor Binding

Distribution of Inhaled m-Xylene in Rat Brain and its Effect on GABAA Receptor Binding: Takehiko ITO, et al. Faculty of Education, Okayama University—Organic solvents generally depress the central nervous system (CNS), similarly to volatile anesthetics. The precise mechanism of their action on the CNS, however, is not fully understood, and remains to be clarified. This study is focused on how inhaled m-xylene distributes in the brain, and whether region specific change in GABA A receptor binding takes place due to the exposure. To conduct this study, we first developed a simple exposure system suitable for inhalation experiments with small animals. Using this system, six-week-old male Sprague-Dawley rats were exposed to m-xylene vapor (2000 ppm) 4 h/d, for 5 consecutive days. At the end of the exposure, m-xylene levels in four different regions of the brain were measured by head-space gas chromatography. Also 14 μm-thick frozen sections of the brain were made, and [35S] t-butylbicyclophosphorothionate (TBPS) binding autoradiography was performed. Uneven distribution of m-xylene in the brain was observed. The concentration in the cerebellum (976 ± 93.4 μg/g tissue) was the highest, while that in the cerebral cortex (467 ± 43.6 μg/g tissue) was the lowest. [35S]TBPS binding was significantly greater in the molecular layer of the cerebellum (control: 12.6 ± 0.64, m-xylene 16.0 ± 1.34 fmol/mg tissue). These results suggest that m-xylene is distributed unevenly in the rat brain, and acute exposure to m-xylene at a high concentration alters [35S]TBPS binding, which may reflect changes in GABA A receptor characteristics. (J Occup Health 2002; 44: 69–75)