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D M Witt

Publications and source records attributed to D M Witt.

30 records · Page 2Linked to original sources

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.

Analgesia↗

Homologous regulation of brain oxytocin receptors.

Specific receptors for oxytocin have been identified in rat forebrain. Previous studies have demonstrated that in select regions, these receptors are dependent on heterologous induction by gonadal steroids. To investigate whether brain oxytocin receptors are homologously regulated by oxytocin, we measured oxytocin receptor binding after hypothalamic paraventricular nucleus lesions, repeated central injections of oxytocin, and continuous central infusion of oxytocin via osmotic minipump. Neither lesions of the paraventricular nucleus nor repeated oxytocin injections altered the binding of the selective oxytocin receptor ligand [125I]OTA [125I] d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)] ornithine vasotocin, as measured by in vitro receptor autoradiography. After 10 days of continuous oxytocin infusion by osmotic minipump, oxytocin receptor binding decreased in every target field by at least 50%. This decrease appeared to represent a down-regulation of receptors and not displacement by exogenous peptide, as it persisted for at least 24 h after pump removal, and binding remained reduced in the presence of a saturating concentration of [125I] OTA. Reduction of oxytocin receptors in response to increased oxytocin release may represent an important physiological mechanism for the regulation of central oxytocin neurotransmission.

Animals↗

Oxytocin inhibits male sexual behavior in prairie voles.

Intracerebroventricular (ICV) injection of oxytocin (300 ng) produced an immediate cessation in sexual behavior in sexually active male prairie voles (Microtus ochrogaster). Other social behaviors including social contact, aggression, and autogrooming were not significantly affected by oxytocin, but males that received oxytocin ICV, versus injections that missed the ventricles, showed more sleep postures. Sexual behavior remained inhibited for at least 24 hours and was not activated in tests with a novel receptive female. Sexual and social behavior were not significantly altered in animals in which the oxytocin injection missed the ventricles or in saline-treated males. These findings are consistent with the hypothesis that oxytocin plays a role in sexual satiety.

Animals↗

A selective oxytocin antagonist attenuates progesterone facilitation of female sexual behavior.

Although previous studies have demonstrated that exogenous administration of oxytocin (OT) enhances sexual receptivity in female rats, there is no compelling evidence that endogenous OT has a physiological role in the regulation of female sexual behavior. In the current studies we centrally administered d(CH2)5[Tyr(Me)2Thr4,Tyr-NH2(9)]ornithine vasotocin (or OTA), a selective OT receptor antagonist, to block endogenous OT in ovariectomized females primed with different levels of gonadal steroids. After OTA administration (100-1000 ng), females primed with estradiol benzoate (EB; 1 microgram) and progesterone (P; 250 micrograms) showed reductions in both receptive and proceptive behaviors. These effects of OTA were also evident, though less striking, in females primed with higher doses of EB (10 micrograms) and P (250 micrograms), but significant OTA effects were absent in females primed with EB (10 micrograms) alone. Thus, OTA appeared to attenuate P's facilitation of sexual behavior. Surprisingly, these behavioral effects of OTA administration were not apparent immediately, but emerged only when OTA was given with P 4-6 h before behavioral testing. To determine if these delayed, but lasting, behavioral effects were associated with OTA occupancy of the OT receptor, we measured OT receptor binding ex vivo using receptor autoradiography. Six hours after intracerebroventricular administration of OTA (1000 ng), OT receptor binding was reduced at least 75% in the ventromedial nucleus of the hypothalamus relative to control levels of binding. Thus, those OT receptors previously implicated in the regulation of sexual receptivity appear to be significantly blocked throughout the period of OTA's behavioral effects. Together, these studies lend support to the hypothesis that endogenous OT has a physiological role in the regulation of female sexual behavior.

Animals↗

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)

Animals↗

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.

Animals↗

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.

Animals↗

Estrogen and the induction of lordosis in female and male prairie voles (Microtus ochrogaster).

Estrogen elicited lordosis in ovariectomized female prairie voles (Microtus ochrogaster). Treatment with estradiol benzoate (EB) was particularly effective if administered as multiple injections. Very high dose levels were not, in general, any more effective than lower doses. Individual animals typically showed lordosis within 24 to 48 hr following the onset of EB treatment and prolonged treatments did not increase the percentage of females responding to EB. Castrated male prairie voles did not respond with lordosis to repeated daily injections of 10 micrograms EB given for a period of 15 consecutive days.

Animals↗

Male stimuli are necessary for female sexual behavior and uterine growth in prairie voles (Microtus ochrogaster).

In reproductively naive female prairie voles (Microtus ochrogaster) direct contact with male urine or housing in a male-soiled cage, in the absence of physical contact, resulted in increased uterine weights, but did not reliably elicit behavioral estrus (defined by lordosis). Physical contact with an unfamiliar male, for 1 hr or more, followed by 30 or 48 hr of continuous access to a male-soiled cage, induced lordosis in approximately two-thirds of the females tested. When females were physically exposed to a male for 18 hr and tested 6 hr later, 70% showed lordosis. However, when females receiving either 1 or 18 hr of male contact were removed from the presence of the male and placed in a clean cage for 24 hr, only 29-37% of the females subsequently showed lordosis. These results suggest that direct physical contact with the male or chemical stimuli from the male may be necessary to induce and maintain behavioral estrus in female prairie voles.

Animals↗

Neonatal decortication and adult female sexual behavior.

Neonatal lesions of the cerebral cortex in female rats did not eliminate female sexual behavior as measured by lordosis. However, lordosis in response to prolonged low levels of estradiol benzoate (1.0 micrograms/day for 6 days) was attenuated in lesioned females. Following estradiol benzoate plus progesterone (0.5 mg) treatment the probability of lordosis increased markedly in the decorticate females, but still remained below control levels. Decorticate females were mounted by the male at least as often as control females. Hopping and darting and rejection behaviors on the part of the female were virtually eliminated in the decorticate group. However, these females continued to direct sniffing behavior toward the male at levels above those of the controls.

Animals↗

Dornase alfa: a new option in the management of cystic fibrosis.

Recombinant human DNase I, or dornase alfa, is the first new therapy developed specifically for cystic fibrosis in almost 30 years. It selectively digests extracellular DNA and reduces the viscosity of purulent sputum. In clinical trials dornase alfa modestly improved pulmonary function, slightly decreasing the number of respiratory exacerbations requiring parenteral antibiotics compared with placebo. Phase III studies suggest that patients receiving dornase alfa also spend slightly fewer days in the hospital than those treated with placebo. The aerosolized preparation is safe and generally well tolerated. Voice alteration and sore throat are the most commonly reported adverse effects. Further research is necessary to determine the optimum time to initiate therapy and to evaluate the agent's pharmacoeconomic impact on the treatment of cystic fibrosis. Aerosolized dornase alfa should always be given in conjunction with standard cystic fibrosis therapies including antibiotics, chest physiotherapy, and pancreatic enzyme supplementation.

Administration, Inhalation↗