GABA/benzodiazepine receptors in the ventromedial hypothalamic nucleus regulate both anxiety and panic-related defensive responses in the elevated T-maze

Abstract

It has been shown that facilitation of GABA-mediated neurotransmission in the medial nucleus of the amygdala and the dorsal periaqueductal gray (dPAG) inhibits the escape, but not the inhibitory avoidance response generated in the elevated T-maze test of anxiety (ETM). These defensive behaviors have been associated with panic and generalized anxiety, respectively. Previous evidence indicates that the dorsomedial part of the ventromedial hypothalamus (VMHdm), which is interconnected with these two brain areas, is also part of the neurobiological substrate controlling escape behavior. In the present study, we investigated in male Wistar rats whether the intra-VMHdm injection of GABA-modulating drugs differently affect the two defensive tasks measured in the ETM. The results showed that the microinjection of the benzodiazepine (BZD) receptor agonist midazolam (10, 20 and 40 nmol), the GABA A receptor agonist muscimol (2, 4 and 8 nmol) or the GABA B receptor agonist baclofen (2, 4 and 8 nmol) impaired inhibitory avoidance and escape performance, an anxiolytic and panicolytic-like effect, respectively. On the other hand, local administration of the BZD inverse agonist FG 7142 (20, 40 and 80 pmol) facilitated both behaviors, suggesting anxiogenic and panicogenic-like effects. These results were not due to motor alterations, since the drugs did not affect exploratory behavior in an open field. The data suggest that GABA A/BZD and GABA B receptors within the VMHdm are involved not only in the control of panic-related, but also of anxiety-related behaviors.