Histaminergic neurons mediate restraint stress-induced activation of central 5-hydroxytryptaminergic neurons in the rat.

The role of histamine in mediating restraint stress-induced increases in the activity of central 5-hydroxytryptaminergic neurons was evaluated in male rats. 5-Hydroxytryptaminergic neuronal activity was estimated by measuring concentrations of the 5-hydroxytryptamine (5-HT) metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the nucleus accumbens and suprachiasmatic nucleus which contain terminals of these neurons. Placement of rats within restraining tubes rapidly increased (within 10 min) 5-HIAA concentrations in the nucleus accumbens and suprachiasmatic nucleus. Depletion of neuronal histamine by alpha-fluoromethylhistidine or antagonism of histamine H1 receptors by mepyramine prevented stress-induced increases in 5-HIAA concentrations, whereas blockade of histamine H2 receptors by zolantidine was without effect. Neither alpha-fluoromethylhistidine, mepyramine nor zolantidine affected basal 5-HIAA concentrations in either brain region. These results indicate that histaminergic neurons mediate stress-induced increases in the activity of central 5-hydroxytryptaminergic neurons via an action at histamine H1 receptors.