Role of glutamate ionotropic and benzodiazepine receptors in the ventromedial hypothalamic nucleus on anxiety

The dorsomedial part of the ventromedial hypothalamic nuclei (VMHdm) has been related to the modulation of defensive behavior in mammals. The objective of the present study was to test the hypothesis that administration into the VMHdm of midazolam, a benzodiazepine receptor full agonist, or AP7, a glutamate NMDA receptor antagonist, would produce anxiolytic effects in the elevated plus-maze (EPM) or the Vogel's punished licking tests. Male Wistar rats with unilateral cannulae aimed at the VMHdm received intra-cerebral injections of midazolam (15-60 nmol/0.25 μL), AP7 (0.2-2 nmol/0.3μL) or saline and were submitted to the behavioral tests. Midazolam (30 nmol) increased the percentage of time spent in open arms of the EPM. AP7, on the other hand, decreased open and enclosed arm exploration. In the Vogel test, however, both midazolam (30-60 nmol) and AP7 increased the number of punished licks. Histological control experiments found no significant effects when the drugs were injected into the nearby lateral hypothalamic area. These results suggest that facilitation of gabaergic or antagonism of glutamatergic neurotransmission in the VMHdm can produce anxiolytic-like effects.