Stimulation of benzodiazepine receptors in the dorsal hippocampus and median raphe reveals differential GABAergic control in two animal tests of anxiety

The effects of pharmacological challenges to the benzodiazepine receptors i n the dorsal hippocampus and median raphe nucleus were investigated in the social interaction and the elevated plus-maze tests of anxiety in rats. In the social interaction test, bilateral administration of midazolam (1 and 2 mu g), into the dorsal hippocampus had anxiolytic effects; flumazenil (500 ng) was silent, but was able to antagonize the anxiolytic effects of midaz olam (2 mu g). In the social interaction test, midazolam was also anxiolyti c when infused into the median raphe nucleus; flumazenil (100 and 500 ng) i ncreased locomotor activity, but did not change anxiety measures. As an ana tomical control, midazolam (1 and 2 mu g) was infused into the adjacent pon tine reticular nucleus, and was without effect. In contrast to the social i nteraction test, local infusion of midazolam (1 and 2 mu g) and flumazenil (100 and 500 ng) into either the dorsal hippocampus or the median raphe nuc leus failed to change anxiety measures in the elevated plus-maze (trials 1 and 2), These results show that stimulation of the benzodiazepine receptors in the hippocampus or the median raphe nucleus leads to anxiolytic effects in the social interaction test, but not in the elevated plus-maze. It woul d therefore appear that the two tests detect different types of anxiety tha t are differentially modulated by GABA(A)-benzodiazepine receptors in the d orsal hippocampus and the median raphe nucleus.