Alterations in GABAergic function following forced swimming stress.

Forced swimming induces alterations in the GABA brain concentration and could change the sensitivity of the GABA/benzodiazepine receptor-chloride ionophore complex to benzodiazepines. This change in sensitivity could be explained by the allopregnanolone release that takes place during stress. The current study was carried out to determine whether forced swimming is able to modify the anti-anxiety effect of diazepam and to explore the possible relation of this change to allopregnanolone, the GABA concentration or/and the GABA/benzodiazepine receptor density. Unstressed and stressed mice, injected with the vehicle or diazepam, were evaluated in the exploratory behavior test. Diazepam induced clear anxiolytic actions at all doses in unstressed animals, but such an effect was not observed in stressed animals. The injection of allopregnanolone 24 h before the anxiety test blocked the effect of this benzodiazepine. Forced swimming decreased GABA concentrations in the hippocampus and the thalamus-hypothalamus region, besides decreasing the [(3)H]flunitrazepam labeling in both the hypothalamus and amygdala. These results show that forced swimming abolishes the anti-anxiety effect of diazepam.