Histaminergic neurons mediate restraint stress-induced increases in the activity of noradrenergic neurons projecting to the hypothalamus.

The role of histamine in mediating restraint stress-induced increases in the activity of noradrenergic neurons projecting to the hypothalamus was evaluated in male rats. Noradrenergic neuronal activity was estimated by measuring concentrations of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) in the paraventricular and medial preoptic nuclei which contain terminals of these neurons. Placement of rats within restraining tubes rapidly increased MHPG but not norepinephrine concentrations in the paraventricular and medial preoptic nuclei. Depletion of neuronal histamine by alpha-fluoromethylhistidine and antagonism of H1 receptors by mepyramine attenuated, whereas blockade of H2 receptors by zolantidine did not prevent the stress-induced increases in MHPG concentrations. Neither mepyramine nor zolantidine affected MHPG concentrations in hypothalamic regions of nonstressed rats. These results indicate that histaminergic neurons contribute to the stress-induced increase the activity of noradrenergic neurons projecting to the hypothalamus via an action at H1 receptors.