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.