Influence of forced swimming-induced stress on the anxiolytic-like effect of 5HT_1A agents in mice

Rationale: Stress has been related to both anxiety and mood disorders. Forced swimming (FS) is a type of stress that is able to modify the activity of serotonin (5-HT) and GABA in the central nervous system. 5-HT_1A compounds have been shown to be anxiolytic in a variety of behavioral models and in clinical studies. Objective: The main purpose of the present study was to analyze the effect of FS on the anxiolytic-like actions of three 5-HT_1A compounds. Methods: Stressed (ST) and unstressed (UST) mice were evaluated in the exploratory behavior test (EBT) or burying behavior test (BBT). In addition, the action of increasing doses of the 5-HT_1A compounds buspirone, 8-OH-DPAT and indorenate in ST and UST mice was analyzed using the EBT. A spontaneous ambulatory behavior test was carried out immediately after the anxiety tests. Results: One session of FS induced anxiolytic-like behavior in mice tested in both the EBT and the BBT. This effect of FS was blocked by a previous administration of either picrotoxin or WAY 100635. The 5-HT_1A compounds produced a clear anxiolytic-like effect in UST animals. By contrast, with low doses of either 8-OH-DPAT (0.01 mg/kg), buspirone (0.03 mg/kg) or indorenate (0.3, 0.6 mg/kg) ST mice showed a decrease in the anti-anxiety-like effect observed after FS. No change in ambulation that could mask the results of the anxiety test was registered. Conclusions: The present data provide evidence that FS induces changes in the effect of 5-HT_1A agents. The participation of the 5-HT and/or GABA systems in these stress-induced effects is discussed.