ROLE OF THE DORSOMEDIAL HYPOTHALAMUS IN THE CARDIOVASCULAR-RESPONSE TO STRESS

1. Disinhibition of the dorsomedial hypothalamus (DMH) in rats by loca l microinjection of GABA(A) receptor antagonists evokes behavioural an d physiological changes resembling those seen in acute experimental st ress. 2. Conversely, similar microinjection of muscimol, a potent agon ist at inhibitory GABA(A) receptors, virtually abolishes stress-induce d increases in heart rate and arterial pressure. 3. Blockade of excita tory amino acid (EAA) receptors in the DMH also attentuates stress-ind uced cardiovascular changes and microinjection of kainate, AMPA or NMD A at low doses elicits cardiovascular effects resembling those seen in stress. Paradoxically, injection of higher doses of NMDA or of glutam ate into this region has no consistent effect. 4. The cardiovascular e ffects of bicuculline methiodide, a GABA(A) receptor antagonist, as we ll as those of NMDA and/or kainate were assessed after identical injec tion into either the DMH, the paraventricular nucleus (PVN) or the are a between the two nuclei in both anaesthetized and conscious rats. For each agent, a similar pattern was seen, with the largest increases in heart rate and arterial pressure occurring after injection into the D MH and the smallest changes resulting from injection into the PVN. 5. In a parallel study, bilateral microinjection of muscimol into the DMH dramatically reduced air stress-induced cardiovascular changes; simil ar injection into the area of the PVN had no effect, while injection i nto the area between the nuclei produced an intermediate effect. 6. Ou r findings suggest that activation of neurons in the region of the DMH mediates stress-induced cardiovascular changes and that the activity of these neurons may be determined by the balance of tone at inhibitor y GABA(A) receptors and EAA receptors.