Immunohistochemical localization of toluene-induced c-Fos protein expression in the rat brain

Although toluene is a widely abused substance, the neuronal populations and pathways mediating its effects are not well understood. Using c-Fos protein as a marker for neuronal activation, the present study investigated the pattern of c-Fos induction at 1h after various doses (0, 300, 750, and 1000 mg/kg, i.p.) of toluene injection in adult male rats. Quantitative analysis of Fos-immunoreactive neurons indicated toluene dose-related induced c-Fos immunoreactivity in the majority of structures examined. The structures included several cortex subareas (primary motor cortex, secondary motor cortex, somatosensory cortex, frontal association cortex, cigulate cortex area 1, cigulate cortex area 2, prelimbic cortex, infralimbic cortex, retrosplenial agranular cortex, ventral orbital cortex, lateral orbital cortex, and piriform cortex), ventral tegmental area, nucleus accumbens shell, thalamic nuclei (mediodorsal, lateral posterior, and laterodorsal ventrolateral) and pontine nuclei. However, the substantia nigra, caudate putamen, nucleus accumbens core, subthalamic nucleus, hippocampus and cerebellum were almost unaffected. The data demonstrate that toluene dose-related induced a unique pattern of c-Fos immunoreactivity. The widespread distribution of toluene-induced c-Fos expression seen in this study can be linked to the profound alterations in physiological function and behavior produced by this solvent.