5-HT1A receptor activation counteracts c-Fos immunoreactivity induced in serotonin neurons of the raphe nuclei after immobilization stress in the male rat

The serotoninergic system and the 5-HT1A receptors have been involved in the brain response to acute stress. The aim of our study was evaluate the role of the 5-HT1A receptors in serotoninergic cells of rostral and caudal raphe nuclei under acute immobilization in rats. Double immunocytochemical staining of 5-hydroxy-tryptamine and c-Fos protein and stereology techniques were used to study the specific cell activation in the raphe nuclei neurons in five groups (control group, immobilization group (immobilization lasting 1 h), DPAT group (8-OH-DPAT 0.3 mg/kg, s.c.), DPAT + IMMO group (8-OH-DPAT 0.3 mg/kg, s.c., 30′ prior acute immobilization) and WAY + DPAT + IMMO group (WAY-100635 0.3 mg/kg, s.c. and 8-OH-DPAT 0.3 mg/kg, s.c., 45′ and 30′, respectively, before immobilization). Our results showed an increase in the number of c-Fos immunoreactive nuclei in serotoninergic cells in both dorsal and median raphe nuclei in the immobilized group. The 8-OH-DPAT pretreatment counteracted the excitatory effects of the acute immobilization in these brain regions. In addition, WAY-100635 administration reduced the effect of 8-OH-DPAT injection, suggesting a selective 5-HT1A receptor role. Raphe pallidus and raphe obscurus did not show any differences among experimental groups. We suggest that somatodendritic 5-HT1A receptors in rostral raphe nuclei may play a crucial role in both mediating the consequences of uncontrollable stress and the possible beneficial effects of treatment with 5-HT1A receptor agonists.