The role of the hippocampus and 5-HT/GABA interaction in the central effects of benzodiazepine receptor ligands

The effects of an intrahippocampal administering of a non-selective full (m idazolam), a partial benzodiazepine (BDZ) receptor agonist (bretazenil), an d a BDZ(1) selective (zolpidem) receptor ligand were examined in the open f ield test (OFT) of neophobia and Vogel's test (VT) of conflict behavior in rats. Moreover, the influence of local injections of a non-competitive GABA (A) receptor antagonist, picrotoxin, on the anxiolytic-like effect of serot onin (5-HT) depletion (p-chlorophenylalanine, p-CPA) in the Vogel test was studied. It was found that in the OFT only midazolam (0.1 mu g/site) given to the hippocampus (HP) disinhibited rat exploratory behavior, whereas all the examined compounds inhibited animal motor activity when injected locall y at 10.0 mu g/site, the highest dose used in the tests. In the VT, again, only midazolam disinhibited rat conflict behavior on a dose-dependent basis . Picrotoxin administered to the HP produced a tendency to increase locomot or activity in rats, and significantly attenuated the anti-conflict action of serotonin depletion without changing the pain threshold and spontaneous drinking of the animals, p-CPA induced potent, dose-dependent and selective 5-HT and 5-hydroxyindoleacetic acid decrease in the HP after administering the dose used in the behavioral experiment. Thus, the present data provide evidence for the lack of selective anxiolytic activity of a partial non-se lective agonist and a full selective agonist at the BDZ(1) receptor after t heir administration to the HP. The model of intra-HP drug injections appear ed effective in discriminating the anxiolytic spectrum of activity of new p sychotropic compounds. Moreover, the obtained results indicate that the dor sal HP is one of the central sites important for GABA /5-HT interaction tha t modulates rat emotional behavior.