Diane M. Witt

Enhanced social interactions in rats following chronic, centrally infused oxytocin.

Most studies investigating the behavioral effects of centrally administered oxytocin (OT) have been confined to single acute injections followed by brief behavioral observations lasting up to 90 min. The present study examines the behavioral effects of chronic, centrally administered OT in male rats observed continuously for prolonged periods of time. Either artificial cerebrospinal fluid or OT was centrally infused (via osmotic minipump) to gonadally intact male rats. Behavioral observations were made on males paired with either ovariectomized or estrous females during a 6-h time period. Most striking was the observation that durations of physical contact were doubled in pairs containing OT-infused males, even in the absence of sexual interactions. Also, OT-infused males showed significantly higher levels of anogenital sniffing of females and autogrooming; however, sexual interactions were unaffected by chronic OT. Chronic OT had no effect on body temperature, analgesia, or exploratory behavior in an open field. These findings suggest that chronic OT in male rats has behavioral effects that may significantly enhance adult social (nonsexual) interactions, possibly through alterations in olfactory and somatosensory information processing.

Oxytocin and Social Bonding

The prairie vole is an excellent model for examining the neurobiology of social attachment, and in particular of pair-bond formation. In female prairie voles either sexual interactions or oxytocin infusions can hasten the formation of a partner preference. These results implicate oxytocin in the formation of adult heterosexual social bonds. In conjunction with work on other social systems described in this volume, these findings also support the suggestions of Klopfer and Newton that oxytocin may be important in coordinating mammalian social interactions with other critical reproductive events such as birth, lactation, and sexual behavior.

Central and peripheral effects of oxytocin administration in prairie voles (Microtus ochrogaster)

The present study examined the hypothesis that oxytocin (OT) may influence female sexual behavior in prairie voles (Microtus ochrogaster). The effectiveness of OT to induce sexual behavior was tested in ovariectomized females that were injected daily with estradiol benzoate (EB, 0.02 micrograms, twice), a dose insufficient for estrus induction. On the third day females received intracerebroventricular (ICV) injections of OT (1, 300, or 1000 ng) or saline vehicle. In the presence of minimal estrogen stimulation, OT did not induce sexual receptivity, or influence autogrooming or other social interactions. The behavioral effects of OT were examined in another group of ovariectomized females that received daily oil or EB injections (10 micrograms, twice) followed on the third day by either ICV (1, 300, or 1000 ng) or intraperitoneal (IP) (1, 3, or 10 micrograms) injections of OT. Among EB-treated females, only those in confirmed estrus, prior to ICV or IP injection, were included in these studies. There was a dose-related decrease in the percentage of females that remained in behavioral estrus after ICV OT. In those females that continued to show sexual behavior, lordosis frequencies and durations were unaffected by ICV OT. Nonsexual behavior did not differ between mated females and those exhibiting OT-inhibited sexual behavior. In females that were EB-treated, autogrooming and side-by-side behavior increased after ICV OT, while there was a decline in aggression. Female sexual and nonsexual behaviors were not significantly affected by IP OT.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased Fos Expression in Oxytocin Neurons Following Masculine Sexual Behavior

Induction of the c‐fos protein product (Fos) was used to immunocytochemically identify oxytocin (OT) neurons that may be activated during copulatory interactions. Fos induction was quantified in sexually‐experienced male rats after either (a) exposure to a testing arena recently vacated by an estrous female, (b) copulatory interactions such as mounting and intromission without ejaculation, or (c) mounting and intromissions culminating in ejaculation. In the parvocellular regions of the paraventricular nucleus of the hypothalamus (PVN), the number of neurons expressing Fos increased following either intromission (53%) or ejaculation (124%). Significant, but less striking, increases in the number of cells expressing Fos were noted in magnocellular regions of the PVN where intromission resulted in a 13% increase and ejaculation in a 49% increase in Fos. The number of perikarya immunoreactive for OT and AVP did not differ as a function of increasing sexual contacts. In control (novel arena) males, 33–73% of the Fos labeling occurred in OT cells. Sexual interactions did not enhance the number of double‐labeled cells in most parvocellular regions. However, in lateral parvocellular regions located in the most caudal aspects of the PVN, 31% of the Fos‐positive cells occurred in OT neurons in ejaculated males, while in control males none of the OT cells were double‐labeled. This PVN subdivision is known to consist of neurons that project to the brain stem and spinal cord at lumbar levels which contain motor neurons that regulate penile reflexes. The present data suggest a possible neurochemical circuit which incorporates oxytocinergic neurons in the mediation of masculine sexual responses.

Gonadal Steroids have Paradoxical Effects on Brain Oxytocin Receptors

Specific brain receptors for oxytocin have been described in several mammalian species. The distribution of these receptors differs greatly across species and in the rat, receptor binding in specific brain regions appears to depend upon gonadal steroids. This study used in vitro receptor autoradiography to examine the effects of testosterone on oxytocin receptor binding in the mouse forebrain. Three groups of male mice were compared: castrates treated with blank capsules, castrates treated with testosterone filled capsules, and intact males. Irrespective of steroid treatment, the distribution of oxytocin receptors in mouse forebrain differed markedly from patterns previously described in the rat. In addition to these species differences in receptor distribution, testosterone had effects in the mouse which differed from the induction of receptors previously reported in the rat. In the mouse ventromedial nucleus of the hypothalamus, binding in the untreated castrate males was approximately double that observed in either the intact or the testosterone‐treated castrates. In other regions of the mouse brain, such as the intermediate zone of the lateral septum, binding to oxytocin receptors was increased with testosterone treatment. These results suggest that the brain oxytocin receptor varies across species not only in its distribution but also in its regional regulation by gonadal steroids. These apparently paradoxical changes in oxytocin receptor binding may result from either direct or indirect effects of gonadal steroids in mouse brain.

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

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 [125l]d(CH2)5[Tyr(Me)2,Tyr‐NH29]ornithine vasotocin ([125I]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 μg) 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, [125I]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.

Progesterone modulation of androgen-dependent sexual behavior in male rats

The present study examines the effects of physiological levels of progesterone (P) on copulatory behavior in sexually naive male rats. Two weeks after gonadectomy males were implanted with either empty Silastic capsules (BL) or Silastic capsules containing testosterone (T), P, or both (P+T). When tested with an estrous female, all of the gonadally intact males (intact) and none of the BL controls exhibited mounting/intromission behaviors. Mounting was observed in 75% of the T-alone males. More than half (64%) of the P-alone males and 100% P+T males exhibited mounting. In most cases, mounting was followed by intromission responses. Subsequently, intact and gonadectomized males received daily injections of the P antagonist RU486 along with hormone treatment. After receiving RU486, only 63% of the intact males and 71% of the T-alone males mounted successfully. The facilitatory effects of P on copulatory behavior were completely abolished by RU486 treatment. The present studies provide the first evidence in mammals suggesting that P-dependent mechanisms influence neurochemical pathways involved in copulation.

Hormonal Correlates of Sexual-Behavior and Ovulation in Male-Induced and Postpartum Estrus in Female Prairie Voles:

The purpose of the present study was a description of hormonal profiles in female prairie voles (Microtus ochrogaster) in estrus that was induced by male exposure versus postpartum estrus. Hormonal profiles are reported in sexually naive females and in sexually experienced females, as a function of varying amounts of coital stimulation and as a function of time since male exposure. Ovarian estradiol levels, uterine weights and uterine protein levels increased in virgin females after exposure to a male, were highest in females that showed lordosis, declined slowly when estrous females were isolated from males and decreased sharply following mating. Ovarian progesterone levels increased more rapidly following mating in females in male-induced estrus than in females in postpartum estrus. Serum progesterone levels did not increase significantly within 24 hr following mating, but were elevated by 72 hr after mating. These findings are discussed as they relate to the hormonal control of female sexual behavior.

Effects of hormonal, sexual, and social history on mating and pair bonding in prairie voles.

The interactive effects of hormones, sexual history and cohabitation on sexual and social behaviors were examined in pairs of ovariectomized female and sexually experienced male prairie voles (Microtus ochrogaster). Monitoring with time lapse video tape revealed that females in estradiol benzoate (EB)-induced estrus, and their male partners engaged in high levels of sexual activity which continued intermittently for at least 3 days (until observations were arbitrarily terminated). In conjunction with other studies, these results indicate that the hormonal condition of the female at the time of testing is a major determinant of sexual activity. Prior hormonal, copulatory, or cohabitation experience did not significantly influence sexual responses between females and unfamiliar male partners. However, affiliative behaviors, such as side by side contact, were higher in pairs that were familiar due to prior sexual and cohabitational experience. These results indicate that social and sexual behaviors are independently regulated. Other behaviors, including nasogenital investigation and autogrooming were influenced by the hormonal and sexual history of the female. The implications of these behavioral patterns for reproductive activation, pair bonding, and incest avoidance are discussed.

Patterns of behaviour during postpartum oestrus in prairie voles, Microtus ochrogaster

Abstract Social and sexual behaviour during postpartum oestrus in prairie voles was monitored using time-lapse videotaping over a period of at least 24h. Behaviour was measured as a function of the familiarity and social history of the male partner and as a function of the presence or absence of pups. In general, postpartum oestrus was shorter than male-induced oestrus. When pups remained with the pair, the duration and frequencies of copulatory interactions were further reduced. In familiar pairs mountlordosis bouts were more frequent, and durations of male autogrooming and side-by-side contact were longer than in unfamiliar pairs. All pairs successfully reproduced and litter size among groups was similar, even then the frequency of sexual activities was very low. These results suggest that in monogamous species, such as prairie voles, the social history of the pair was well as female reproductive status are strong determinants of sexual and social interactions that occur during postpartum oestrus.