Inhalation of Low Concentrations of Toluene Induces Persistent Effects on a Learning Retention Task, Beam-Walk Performance, and Cerebrocortical Size in the Rat

Abstract

The organic solvent toluene is widely used in industry. The threshold limit value for extended occupational exposure to toluene is presently set to 200 ppm in the United States. We have investigated the effect of an inhalation exposure of 80 ppm for 4 weeks (6 h/day, 5 days/week), followed by a postexposure period of at least 4 weeks, on behavior and brain features in the rat. Toluene exposure appeared to affect spatial memory, since toluene-exposed rats showed a longer time in the correct quadrant in a Morris swim maze. This effect may indicate that the exposed rats used their praxis strategy longer before they started to look for the platform elsewhere. Toluene-exposed rats showed trends for increases in both locomotion and rearing behaviors and a significantly reduced beam-walk performance. The area of the cerebral cortex, especially the parietal cortex, was decreased by 6–10% in toluene-exposed rats, as shown by magnetic resonance imaging of living rats and autoradiograms of frozen brain sections. The KD and Bmax values of the dopamine D3 agonist [3H]PD 128907 were not affected by toluene, as measured in caudate-putamen and subcortical limbic area using biochemical receptor binding assays and in caudate-putamen and islands of Calleja using quantitative receptor autoradiography. Hence, previously demonstrated persistent effects by toluene on the binding characteristics of radioligands binding to both D2 and D3 receptors seem to indicate a persistent effect of toluene selectively on dopamine D2 receptors. Taken together, the present results indicate that exposure to low concentrations of toluene leads to persistent effects on cognitive, neurological, and brain-structural properties in the rat.