Alpha₁- and Beta-norepinephrinergic receptors of dorsomedial and ventromedial hypothalamic nuclei modulate panic attack-like defensive behaviour elicited by diencephalic GABAergic neurotransmission disinhibition

Gamma-aminobutyric acid (GABA) disinhibition in medial hypothalamus (MH) nuclei of rats elicits some defensive reactions that are considered panic attack -like behaviours. Recent evidence showed that the norepinephrine-mediated system modulates fear -related defensive behaviours organised by MH neurons at least in part via noradrenergic receptors recruitment on midbrain tegmentum. However, it is unknown whether noradrenergic receptors of the MH also modulate the panic attack -like reactions. The aim of this work was to investigate the distribution of noradrenergic receptors in MH, and the effects of either alpha(1)-, alpha(2)- or beta-noradrenergic receptors blockade in the MH on defensive behaviours elaborated by hypothalamic nuclei. Defensive behaviours were evaluated after the microinjection of the selective GABA(A) receptor antagonist bicuculline into the MH that was preceded by microinjection of either WB4101, RX821002, propranolol (alpha(1)-, alpha(2)- and beta-noradrenergic receptor selective antagonists, respectively), or physiological saline into the MH of male Wistar rats. The alpha(1)-, alpha(2)- and beta-noradrenergic receptors were found in neuronal perikarya of all MH nuclei, and the alpha(2)-noradrenergic receptor were also found on glial cells mainly situated in the ventrolateral division of the ventromedial hypothalamic nucleus. The alpha(1)- and beta-noradrenergic receptors blockade in the MH decreased defensive attention and escape reactions elicited by the intra-MH microinjections of bicuculline. These findings suggest that, despite the profuse distributions of alpha(1)-, alpha(2)- and beta-noradrenergic receptors in the MH, both alpha(1)- and beta-noradrenergic receptor- rather than alpha(2)-noradrenergic receptor -signalling in MH are critical for the neuromodulation of panic -like behaviour.