Oxytocin receptor binding in the hypothalamus during gestation in rats

Abstract

Central oxytocin receptors (OTR) may be involved in adaptations of the brain oxytocin (OT) system during gestation, which are critical for systemic release of OT during parturition and lactation. We used quantitative autoradiography to determine changes in OTR binding in numerous brain sites during the course of gestation in the rat. Furthermore, to evaluate the importance of ovarian steroids in mediating pregnancy-related changes in OTR binding, we measured binding in ovariectomized animals treated with progesterone and/or estrogen, and in pregnant animals treated with exogenous progesterone during late gestation. We found that OTR binding was significantly increased in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) by midgestation (day 15) compared with control. In addition, there was a further significant increase in OTR binding in these nuclei by late gestation (day 20). The bed nucleus of the stria terminalis (BNST) and the medial preoptic area (MPOA) also showed significant gestation-associated increases in OTR binding, which were similar during mid- and late pregnancy. Treatment with exogenous progesterone throughout pregnancy did not alter the increase in OTR binding characteristic of late gestation in any of these brain sites. Finally, estrogen treatment in ovariectomized animals resulted in increased OTR binding in the SON, BNST, and MPOA, but not the PVN. These data demonstrate that OTR binding in the hypothalamus is increased during mid- and late-gestation, compared with ovariectomized control animals, which may be mediated by increased estradiol.

Telencephalic binding sites for oxytocin and social organization: A comparative study of eusocial naked mole‐rats and solitary cape mole‐rats

“…These two African mole-rat species display extreme differences in social organization and reproductive strategy. Our objective was to identify species-specific rather than statedependent distribution patterns for OTR binding and oxytocin-containing processes; consequently, because estrogen has been shown to enhance OTR expression at certain central sites in other species (Insel et al, 1993;Kremarik et al, 1995;Broad et al, 1999;Patisaul et al, 2003;Bealer et al, 2006), we restricted the present study to animals with low or undetectable levels of urinary estrogen: adult female mole-rats, which were either subordinate, hypogonadal naked mole-rats or Cape mole-rats during the nonreproductive season (Bennett and Jarvis, 1988;Westlin et al, 1994). Given that species-typical degrees of allomaternal behavior have been shown to be positively correlated with the density of OTR binding in the nucleus accumbens (Olazabal and Young, 2006b) and that naked mole-rats of both sexes are highly alloparental (Jarvis, 1981;Lacey and Sherman, 1991), a parallel, but limited, study was also undertaken on OTR binding in the nucleus accumbens in subordinate, hypogonadal, male naked mole-rats.…”

Oxytocin pathways in the intergenerational transmission of maternal early life stress

“…Extensive research in rodents indicates that OTRs are abundantly expressed within this network rendering it sensitive to the effects of OT (Love, 2014; Numan and Stolzenberg, 2009). Already during the gestational period, the MPOA, which is thought to constitute the core of this network, is hormonally primed, likely through an estrogen (E)-induced upregulation of OTR expression (Bealer et al, 2006; Champagne et al, 2001; Meddle et al, 2007; Numan and Stolzenberg, 2009). This E-primed network is then “triggered” by pup stimuli after parturition to result in immediate onset of maternal behavior, which is then maintained in the postpartum period (Numan and Stolzenberg, 2009; Pedersen, 1997).…”

“…This inhibitory mechanism allows the storage of large amounts of OT in neurohypophyseal large dense-core vesicles necessary to induce labor and immediate postpartum onset of maternal behaviors while simultaneously preventing premature onset of uterus contractions. In addition to hypothalamic OT accumulation, rodent studies show that central OTRs are upregulated during the gestational period (Bealer et al, 2006; Meddle et al, 2007; Young et al, 1997) in brain areas known to be involved in maternal behavior such as the PVN, SON, BNST, and the MPOA. This gestational “priming” of the central maternal attachment system to prepare for onset of maternal behavior immediately after birth is sensitive to the effects of E and could be affected by ELS-exposure (Champagne, 2008).…”

Central blockade of oxytocin receptors during mid-late gestation reduces amplitude of slow afterhyperpolarization in supraoptic oxytocin neurons

“…This suggests that the OTR can be activated at the basal firing rate during the mid-to late gestation period when the OTR binding is significantly increased, even without an elevation in OT release (3). The OTR is a G protein-coupled receptor linked to the phospholipase C pathway (14), and the OT-induced rise in intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) in OT neurons is due primarily to the release of Ca 2ϩ from inositol 1,4,5-trisphosphate (IP 3 )-sensitive stores (11).…”