Time course of the estradiol-dependent induction of oxytocin receptor binding in the ventromedial hypothalamic nucleus of the rat.

Oxytocin (OT) transmission is involved in the steroid-dependent display of sexual receptivity in rats. One of the biochemical processes stimulated by the ovarian steroid 17 beta-estradiol (E2) that is relevant to reproduction is the induction of OT receptor binding in the ventromedial hypothalamic nucleus (VMN). The purpose of these experiments was to determine if E2-induced changes in OT receptor binding in the VMN occur within a time frame relevant to cyclic changes in ovarian steroid secretion. OT receptor binding was measured in the VMN of ovariectomized rats implanted for 0-96 h with E2-containing Silastic capsules. The rate of decay of OT receptor binding was measured in another group of animals 6-48 h after capsule removal. Receptors were labeled with the specific OT receptor antagonist [125I]d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT, and binding was measured with quantitative autoradiographic methods. In addition, plasma E2 levels and uterine weights were assessed in animals from each treatment condition. Significant increases in E2-dependent OT receptor binding and uterine weight occurred within 24 h of steroid treatment. After E2 withdrawal, OT receptor binding and uterine weight decreased significantly within 24 h. These results are consistent with the hypothesis that steroid modulation of OT receptor binding is necessary for the induction of sexual receptivity.

Oxytocin administered centrally facilitates formation of a partner preference in female prairie voles (Microtus ochrogaster).

Prairie voles (Microtus ochrogaster) are monogamous mammals that form male-female pair bonds. Partner preference formation, one component of the pair bond in prairie voles, occurs following male-female cohabitation and is facilitated by mating. The peptide hormone oxytocin is released during physical contact and particularly following vaginal stimulation. Oxytocin has been implicated in mother-infant bond formation. The present study tested the hypothesis that oxytocin participates in the partner preference component of pair bond formation in adult prairie voles. Ovariectomized female prairie voles were implanted with osmotic mini-pumps releasing oxytocin (1-100 ng/h) or artificial cerebrospinal fluid (CSF). Pumps were implanted intracerebroventricularly or subcutaneously and females then were housed for 6 h with a male partner, followed by a preference test in which females could elect to spend time with either the partner or an unfamiliar male. Females in groups that received centrally-administered oxytocin (10 or 100 ng/h), but not CSF, exhibited a significant preference for the partner present during infusion. The induction of a partner preference after oxytocin administration appeared specific for central oxytocin pathways as peripheral oxytocin administration was ineffective. Moreover, central administration of a selective oxytocin receptor antagonist inhibited the behavioral effect of exogenous oxytocin. These results suggest that oxytocin may be one factor contributing to the development of partner preferences in this monogamous rodent.

Projections from the ventromedial nucleus of the hypothalamus contain oxytocin binding sites.

Experiments were conducted to determine the source of steroid-dependent oxytocin (OT) receptors that surround the ventrolateral portion of the ventromedial hypothalamic nucleus (vl-VMN). Ovariectomized rats received sham or unilateral electrolytic lesions of the vl-VMN. Three days later and for the next 4 days, animals were injected with 10 micrograms of estradiol benzoate (EB). OT receptors were labelled with 125I-d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT and binding was assessed with autoradiographic methods. Lesions of the vl-VMN reduced OT receptor binding in the area surrounding the nucleus by over 80% indicating that the majority of OT receptors in the ventromedial hypothalamus are located on fibers originating within the VMN.

Lesions of the hypothalamic paraventricular nucleus disrupt the initiation of maternal behavior.

Electrolytic lesions of the paraventricular nucleus (PVN) of the hypothalamus were found to disrupt the initiation but not the maintenance of maternal behavior in primiparous Sprague-Dawley rats. Following lesions performed on Day 15 of gestation, measures of maternal behavior (grouping, crouching, and nest building), pup retrieval, and pup weight gain were all impaired, but only if the lesion included the most rostral and medial aspects of the PVN. Lesions sparing these regions and sham surgery were generally ineffective. In a separate experiment, PVN lesions performed on Day 4 postpartum had relatively little effect on maternal behavior. As females lesioned prepartum showed changes in open-field behavior as well as maternal behavior, the PVN may be important for modulating responses not only to pups but to several kinds of novel stimuli. These results may also further implicate oxytocin, which is synthesized in the PVN, in the initiation of maternal behavior.

Central administration of corticotropin releasing factor alters rat pup isolation calls.

Rat pups, when socially isolated, emit ultrasonic vocalizations which are believed to indicate distress. This study investigated the effect of intracerebroventricular (ICV) administration of corticotropin releasing factor (CRF) on the production of ultrasonic isolation calls. Following a 2-minute baseline isolation test, rat pups (5-6 days old) were injected ICV with CRF or the CRF antagonist, alpha-helical CRF (9-41). Thirty minutes later, calls were significantly decreased following CRF (0.1 and 0.01 micrograms) and increased following the CRF antagonist (1.0 micrograms). These effects were not explained by changes in locomotor activity, thermoregulation, or plasma glucocorticoid levels following peptide administration. Peripheral administration of CRF (1.0 and 10.0 micrograms) did not alter the number of isolation calls.

A role for central vasopressin in pair bonding in monogamous prairie voles.

Monogamous social organization is characterized by selective affiliation with a partner, high levels of paternal behaviour and, in many species, intense aggression towards strangers for defence of territory, nest and mate. Although much has been written about the evolutionary causes of monogamy, little is known about the proximate mechanisms for pair bonding in monogamous mammals. The prairie vole, Microtus ochrogaster, is a monogamous, biparental rodent which exhibits long-term pair bonds characterized by selective affiliation (partner preference) and aggression. Here we describe the rapid development of both selective aggression and partner preferences following mating in the male of this species. We hypothesized that either arginine-vasopressin (AVP) or oxytocin (OT), two nine-amino-acid neuropeptides with diverse forebrain projections, could mediate the development of selective aggression and affiliation. This hypothesis was based on the following observations: (1) monogamous and polygamous voles differ specifically in the distribution of forebrain AVP and OT receptors; (2) AVP innervation in the prairie vole brain is sexually dimorphic and important for paternal behaviour; (3) central AVP pathways have been previously implicated in territorial displays and social memory; and (4) central OT pathways have been previously implicated in affiliative behaviours. We now demonstrate that central AVP is both necessary and sufficient for selective aggression and partner preference formation, two critical features of pair bonding in the monogamous prairie vole.