Anxiolytic-like and antidepressant-like effects produced by the selective 5-HT6 receptor antagonist SB-258585 after intrahippocampal administration to rats

The purpose of this study was to investigate the effect of SB-258585, a selective 5-HT6 receptor antagonist, administered intrahippocampally to rats, in the conflict drinking and forced swim tests, that is models used for evaluating anxiolytic-like and antidepressant-like activity, respectively. Diazepam and imipramine were used as reference drugs. SB-258585 at a dose of 1 mu g (but not 0.3 and 3 mu g) showed an anticonflict effect that was weaker than that of diazepam (40 mu g). SB-258585 at a dose of 3 mu g (but not 1 and 10 mu g) produced a marked anti-immobility effect comparable with that of imipramine (0.1 mu g). The anxiolytic-like and antidepressant-like activity of SB-258585 seemed to be specific, as that compound - when given by the same route in doses effective in each model - did not affect the shock threshold, nonpunished water consumption, or exploratory activity of rats. The results obtained indicate that the hippocampus is one of the neuroanatomical sites involved in the anxiolytic-like and antidepressant-like activity of the selective 5-HT6 receptor antagonist SB-258585.