Oxytocin Receptor Binding in Female Prairie Voles: Endogenous and Exogenous Oestradiol Stimulation

Abstract

Previous studies have demonstrated that oxytocin receptors in specific nuclei of rat forebrain are regulated by gonadal steroids. The current study used in vitro receptor autoradiography to investigate the distribution and regulation of oxytocin receptors in the forebrain of the female prairie vole (Microtus ochrogaster). In contrast to rats, in female prairie voles gonadal steroid secretion and oestrus behaviour result from male chemosignal stimulation and ovulation is induced by mating. Thus, the prairie vole brain provides an opportunity for investigating links between environmental stimuli, gonadal steroids and oxytocin receptors. Using a selective oxytocin receptor ligand [1'51]d(CH,),[Tyr(Me)',Tyr-NH~]ornithine vasotocin (["51]OTA), specific binding was found in several regions including the anterior olfactory nucleus, the ventromedial nucleus of the hypothalamus, the bed nucleus of the stria terminalis, the amygdala and several cortical areas. Following ovariectomy, oestradiol benzoate (10 pg) administration increased oxytocin receptor binding 100% in the anterior olfactory nucleus, but did not affect receptors in other regions. Gonadallyintact females, exposed to male chemosignals, had significant increases in both endogenous oestradiol levels and anterior olfactory nucleus oxytocin receptor binding relative to gonadally-intact females unexposed to male chemosignals. Following prolonged exposure to males with ad libitum mating, ['251]OTA receptor binding decreased to the levels found in unstimulated females. These results demonstrate that increases in oestrogen levels, of either exogenous or endogenous origin, can modulate oxytocin receptors in the brains of female prairie voles. In contrast to rats, oestrogen in female prairie voles appears to affect receptors in the anterior olfactory nucleus rather than the hypothalamus. We suggest that the species differences in oxytocin receptor distribution and gonadal steroid responsiveness reflect variations in reproductive physiology and possibly behaviour.Several studies have implicated oxytocin in the central mediation of sexual behaviour in female rats. Not only does centrally administered oxytocin enhance sexual receptivity in female rats that are primed with either oestrogen and progesterone ( I , 2) or high levels of oestrogen alone (3), but an oxytocin antagonist attcnuatcs the gonadal steroid induction of lordosis (4). Gonadal steroids appear to regulate several aspects of oxytocin physiology. For instance, fluctuations in oxytocin content, correlated with the oestrous cycle, have been observed in the pituitary ( 5 ) and paraventricular nucleus of the hypothalamus of gonadally-intact fcmalcs (6) and oxytocin increases in portal blood on the afternoon of pro-oestrus prior to the onset of sexual receptivity in female rats (7). Moreovcr, oestrogen selectively increases brain oxytocin receptors and thus sensitizes specific brain areas to oxytocin. In particular, the gonadal steroid induction of oxytocin receptors in the ventromedial nucleus of the hy...

Oxytocin has dose-dependent developmental effects on pair-bonding and alloparental care in female prairie voles

“…There is considerable evidence from between species comparisons that monogamous and nonmonogamous mammals have differences in the distribution of peptide receptors including those for OT and AVP (Witt et al, 1991;Shapiro and Insel, 1992;Insel et al, 1994). In addition, we have observed that early manipulations of OT, even at the lowest dose used here (1 mg/ kg), are capable of producing life-long, sexually-dimorphic changes in peptide receptors (Bales et al, 2007b) .…”

The neurobiology of social attachment: A comparative approach to behavioral, neuroanatomical, and neurochemical studies

“…Given the sexually dimorphic nature of this AVP pathway (Bamshad et al, 1993;Wang, 1995;Wang et al, 1996b) and lack of similar changes in AVP activity in female voles , these data provide correlational evidence of the potential involvement of central AVP in physiological and behavioral processes associated with mating and pair bond formation in male prairie voles (Bamshad et al, 1994;Wang et al, 1994;Wang et al, 1998). In female prairie voles, exposure to male chemosensory cues induced an increase in OTR binding in the anterior olfactory nucleus (Witt et al, 1991), indicating that social behavior can also affect OTRs.…”

Oxytocin: The Great Facilitator of Life

“…or i.p.) do not facilitate sexual receptivity in female prairie voles pretreated with E (Witt et al , 1990), and treatment with an Oxt antagonist does not inhibit sexual behavior (Witt et al , 1991). However, in sexually-naïve females (no exposure to males after weaning), daily Oxt injection (s.c.) for 5 days increases the likelihood of mating (compared to saline treated females), and treatment of Oxt with E increases sexual receptivity greater than E alone (Cushing and Carter, 1999).…”