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 oxytocin (OT) secretion in various physiological conditions, including parturition and lactation. The present studies investigated whether histamine also influences the central intranuclear release of OT, which is known to be important in the activation of OT neurons, and the possible interaction of histamine 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 fluid (ACSF) vehicle, ACSF containing histamine, ACSF containing histamine in combination with a specific H1 or H2 histamine receptor antagonist, or ACSF containing histamine and the alpha-adrenergic antagonist phentolamine. Dialysates and plasma were collected, and OT concentrations were determined using RIA. Dialysis of the PVN with ACSF containing histamine significantly increased the release of OT systemically and centrally within the PVN. Furthermore, the in creases in OT concentration in dialysates and plasma were prevented by simultaneous administration of chlorpheniramine (an H1 receptor antagonist) or ranitidine (an H2 receptor antagonist) as well as by the adrenergic antagonist phentolamine. These data demonstrate that histamine acts within the PVN to increase both systemic and intranuclear release of OT. Furthermore, the increased OT release induced by histamine is dependent upon stimulation of both H1 and H2 histaminergic receptors and subsequent activation of alpha-noradrenergic receptors. These findings suggest that histamine induces systemic and intranuclear OT release by stimulating the release of norepinephrine.