Stimulation of central and systemic oxytocin release by histamine in the paraventricular hypothalamic nucleus: Evidence for an interaction with norepinephrine

Central histaminergic neurons have been implicated in the control of oxytoc in (OT) secretion in various physiological conditions, including parturitio n and lactation. The present studies investigated whether histamine also in fluences the central intranuclear release of OT, which is known to be impor tant in the activation of OT neurons, and the possible interaction of hista mine with norepinephrine in systemic and central OT release. Microdialysis probes were placed immediately adjacent to the hypothalamic paraventricular nucleus (PVN) and used for administration of artificial cerebrospinal flui d (ACSF) vehicle, ACSF containing histamine, ACSF containing histamine in c ombination with a specific H1 or H2 histamine receptor antagonist, or ACSF containing histamine and the alpha-adrenergic antagonist phentolamine. Dial ysates and plasma were collected, and OT concentrations were determined usi ng RIA. Dialysis of the PVN with ACSF containing histamine significantly in creased the release of OT systemically and centrally within the PVN. Furthe rmore, the in creases in OT concentration in dialysates and plasma were pre vented by simultaneous administration of chlorpheniramine (an H1 receptor a ntagonist) or ranitidine (an H2 receptor antagonist) as well as by the adre nergic antagonist phentolamine. These data demonstrate that histamine acts within the PVN to increase both systemic and intranuclear release of OT. Fu rthermore, the increased OT release induced by histamine is dependent upon stimulation of both H1 and H2 histaminergic receptors and subsequent activa tion of alpha-noradrenergic receptors. These findings suggest that histamin e induces systemic and intranuclear OT release by stimulating the release o f norepinephrine.