Roles of 5-HT 1A receptors in the dorsal raphe and dorsal hippocampus in anxiety assessed by the behavioral effects of 8-OH-DPAT and S 15535 in a modified Geller–Seifter conflict model

Abstract

8-OH-DPAT [8-hydroxy-2-(di- N-propylamino)tetralin], a 5-HT 1A receptor agonist, and S 15535 (4-benzodioxan-5-yl)1-(indan-2-yl)piperazine, a partial agonist at 5-HT 1A receptors, were administered into the dorsal raphe nucleus and dorsal hippocampus and their behavioral effects were assessed in a modified Geller–Seifter conflict model. Injected into the dorsal raphe nucleus 8-OH-DPAT, 1 μg but not 0.04 or 0.2 μg 0.5 μl −1, and S 15535, 2.5 μg but not 0.1 or 0.5 μg 0.5 μl −1, significantly increased punished responding with no effect on rates of unpunished or time-out responding. WAY 100635, a selective 5-HT 1A receptor antagonist, injected subcutaneously at 0.3 mg kg −1 30 min before 1 μg 8-OH-DPAT or 2.5 μg S 15535 in the dorsal raphe, completely antagonized their effects on punished responding. At doses ranging from 1 to 10 μg μl −1 injected into the CA1 region of the dorsal hippocampus neither 8-OH-DPAT nor S 15535 modified punished responding or the rates of time-out. At the highest doses, 8-OH-DPAT significantly reduced unpunished responding whereas S 15535 had the opposite effect. The results suggest that stimulation of 5-HT 1A receptors in the dorsal raphe nucleus has anxiolytic-like effects whereas stimulation of postsynaptic receptors in the dorsal hippocampus has no anxiolytic or anxiogenic effects, at least judging from changes in rates of punished responding. These results are compatible with the hypothesis that 5-HT 1A receptor agonists and partial agonists attenuate anxiety by reducing serotonergic transmission in brain areas innervated by the dorsal raphe nucleus.