Anxiolytic homophthalazines increase Fos-like immunoreactivity in selected brain areas of the rat.

Nerisopam, an anxiolytic and antipsychotic homophthalazine induces rapid, intense expression of Fos-like immunoreactivity in the rostral, dorsomedial and lateral parts of the striatum in the rat. Fos-positive cells also occurred in the globus pallidus, the olfactory tubercle and in the accumbens nucleus (in the cone and shell portions) but the substantia nigra, the entopeduncular and the subthalamic nuclei were virtually Fos-negative. 5 h after nerisopam application, however, cells in the reticular zone of the substantia nigra showed Fos-like immunopositivity. After a daily application of nerisopam for two weeks, relatively weak Fos-like immunoreactivity was observed in the striatum and the subthalamic nucleus but not in the globus pallidus. Unilateral surgical transection of the striato-nigral pathway, which depleted tyrosine hydroxylase immunostaining in the ipsilateral striatum did not influence nerisopam-induced Fos-like immunoreactivity in the striatal neurons, either ipsi- or contralateral to the knife cut. Our results suggest that the striatal neurons are the primary targets of this anxiolytic and antipsychotic drug in the central nervous system.