Effects of acute and chronic toluene inhalation on behavior, monoamine metabolism and specific binding (3H-serotonin and 3H-norepinephrine) of rat brain.

The present study deals with the effect of chronic toluene inhalation (30,000-40,000 ppm in air, 15 min/day for 30 days) that induced abnormal behavior states resembling the serotonin syndrome in rats: resting tremor, hindlimb abduction, Straub tail, head weaving and rigidity. The head weaving latencies were significantly decreased when assessed at 15 and 30 days of exposure to toluene vapors. The sequence pattern signs of serotonin syndrome were changed after 15 and 30 days of exposure, indicating possible cumulative effects and/or tolerance development. There were no changes in concentrations of indolamine and catecholamine compounds in different parts of the rat brain (cerebral cortex, midbrain, brainstem and cerebellum) as influence of chronic toluene exposure. Examination of specific serotonin ((3H)-5HT) to crude synaptic membranes prepared from rat brains and subjected to chronic toluene inhalation revealed a very high increased value in apparent Kd (30.7 +/- 15) with respect to its air control (9.7 +/- 2.3) and baseline control (5.8 +/- 3.2). This difference was highly significant (p < 0.02). There were no changes in apparent Bmax of specific (3H)-5HT binding sites. On the other hand (3H)-NE binding of rat brain studies did not show any difference either in apparent Kd or apparent Bmax. These results indicate that serotonin syndrome may be a consequence of changes of serotonergic mechanism, specifically a reduced affinity in specific (3H)-5HT binding sites.