Serotonergic innervation of the hippocampus and nucleus accumbens septi and the anxiolytic-like action of midazolam and 5-HT1A receptor agonists.

An involvement of serotonergic innervation of the hippocampus (HP) and the nucleus accumbens septi (NAS) in anxiolytic activity of benzodiazepine midazolam and 5-HT1A receptor agonists was studied in two different animal models of anxiety. Injection of midazolam (10.0 and 20.0 micrograms) or 8-OH-DPAT (0.5 and 1.0 micrograms) into the hippocampus increased punished consumption of water in the Vogel conflict test. Buspirone given at 0.1, 0.5 and 1.0 microgram was ineffective in the Vogel test, while at 5.0 micrograms it enhanced shock-induced suppression of drinking. In the open-field test midazolam (0.01 and 0.1 microgram), 8-OH-DPAT (0.1, 0.5 and 1.0 microgram) and buspirone (2.5 and 5.0 micrograms) increased the number of entries into the central part of the open-field and the time spent in the central sector. Depletion of 5-HT had no influence on the anxiolytic-like effect in the open-field test of intrahippocampally-administered 8-OH-DPAT (0.5 microgram), but the drug tended to increase motor activity in lesioned animals. Midazolam and buspirone injected into the NAS did not have an anxiolytic effect in the Vogel test. A small increase in punished drinking was observed after 8-OH-DPAT (1.0 and 2.5 micrograms). Following intra-NAS injection, midazolam, 8-OH-DPAT and buspirone all failed to produce any marked anxiolytic-like effect in the open-field test. It appears that the hippocampus, rather than the NAS, is involved in mediating anxiolytic-like effects of 5-HT1A receptor agonists. Hippocampal postsynaptic 5-HT1A receptors may account for the anti-emotional influence of this group of drugs. The results indicate some similarities in the psychotropic profile of 5-HT1A receptor agonists and midazolam.