Differential sensitivity of intranuclear and systemic oxytocin release to central noradrenergic receptor stimulation during mid- and late gestation in rats

Abstract

Differential sensitivity of intranuclear and systemic oxytocin release to central noradrenergic receptor stimulation during mid-and late gestation in rats. Am J Physiol Endocrinol Metab 287: E523-E528, 2004. First published May 18, 2004 10.1152/ajpendo.00572.2003.-A number of changes occur in the oxytocin (OT) system during gestation, such as increases in hypothalamic OT mRNA, increased neural lobe and systemic OT, and morphological and electrophysiological changes in OT-containing magnocellular neurons, suggestive of altered neuronal sensitivity, which may be mediated by ovarian steroids. Because central norepinephrine (NE) and histamine (HA) are potent stimulators of OT release during parturition and lactation, the present study investigated the effects of central noradrenergic and histaminergic receptor activation on systemic (NE, HA) and intranuclear (NE) OT release in pregnant rats and in ovariectomized rats treated with ovarian steroids. Plasma OT levels in late gestation were significantly higher compared with all other groups, and neither adrenergic nor histaminergic receptor blockade decreased these elevated levels. Furthermore, the ␣-adrenergic agonist phenylephrine, but not histamine, stimulated systemic OT release to a significantly greater extent in late gestation than in midpregnant, ovariectomized, or steroid-treated females. Although basal extracellular OT levels in the paraventricular nucleus, as measured with microdialysis, were unchanged during pregnancy or steroid treatment, noradrenergic receptor stimulation of intranuclear OT release was significantly elevated in midgestation females compared with all other groups. These studies indicate that sensitivity of intranuclear and systemic OT release to noradrenergic receptor activation differentially varies during the course of gestation. pregnancy; neurotransmitter; norepinephrine; histamine; estradiol; progesterone PREVIOUS STUDIES HAVE SHOWN that central and systemic oxytocin (OT) release is important during parturition and lactation. OT is synthesized in hypothalamic magnocellular paraventricular (PVN) and supraoptic (SON) nuclei and is released via the neurohypophysis into circulation in response to uterine contractions and mammary gland stimulation (8). OT is also released within the PVN and SON (intranuclear release) (28), which is thought to be critical for initiating and coordinating the firing activities of the magnocellular OT neurons responsible for systemic OT release during parturition and lactation (23,27).A number of changes in the OT system have been documented during late gestation: central OT mRNA is increased (7,26,33,39,41), morphological rearrangements of magnocellular nuclei facilitate increased connectivity of soma and dendrites in OT neurons (37), and electrophysiological changes in OT neuronal firing patterns (18) and in active membrane properties (35) are associated with increases in spontaneous bursting. As a likely consequence of these changes, OT concentrations in the neural lobe (13, 22) and systemic OT release (22...

Endogenous Nociceptin System Involvement in Stress Responses and Anxiety Behavior

“…Peripheral OT secretory responses to psychological stressors are also slightly attenuated in late pregnant rats (Douglas et al, 1995;Neumann et al, 2000), although responses to physical stress such as immune challenge are more restrained. Despite that, OT neurones increase their OT content, dendritic OT efflux of the nuclei slightly increases and OT neurones exhibit increased responsiveness to some stimuli toward the end of pregnancy (Douglas et al, 1995;Leng, Meddle, & Douglas, 2008;Lipschitz, Crowley, & Bealer, 2004). Together with the evidence that OT receptor expression and binding increase in late pregnancy (Bealer, Lipschitz, Ramoz, & Crowley, 2006), including in BNST and amygdala, these data further support a role for OT in gestational anxiolysis.…”

Reversal of Peripheral Nerve Injury-induced Hypersensitivity in the Postpartum Period

“…The observation that pregnancy did not alleviates SNL-induced hypersensitivity is consistent with the fact that oxytocin released in the paraventricular hypothalamic nucleus of pregnant rats did not differ from that of nonpregnant animals. 34 35 Following labor, there is a significant but transient increment of oxytocin in the paraventricular hypothalamic nucleus (3 fold) and during lactation central oxytocin remains high during the postpartum period. 34 It is also consistent with the very transient reduction in withdrawal threshold, even in normal animals, when the pups were weaned at the normal time after delivery.…”

Oxytocin receptor binding in the hypothalamus during gestation in rats

“…These steroid hormone replacement procedures are routinely used by us (32) and others (2-4) as a model for the changing hormonal milieu present during gestation. In these studies, treatment with estrogen alone, or combined estrogen and progesterone both produced significant increases in OTR binding in BNST, MPOA, and the SON.…”

“…We have recently found that central infusion of a selective OT receptor (OTR) antagonist during the final 2 wk of gestation delays the pulsatile release of OT during suckling and impairs pup development during lactation, without altering maternal behavior (31). These data suggest that during gestation, OT exerts central actions that are critical for the normal function and sensitivity of this neuroendocrine system subsequently during lactation.It is possible that these effects are the result of increased release of OT locally within the magnocellular nuclei during gestation, but such increased intranuclear release has not been observed (11,32). Alternatively, there may be changes in OTR expression and/or activation during this time.…”

“…It is possible that these effects are the result of increased release of OT locally within the magnocellular nuclei during gestation, but such increased intranuclear release has not been observed (11,32). Alternatively, there may be changes in OTR expression and/or activation during this time.…”