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Biomedical subjects

James G Pfaus

Publications and source records attributed to James G Pfaus.

17 recordsLinked to original sources
PubMed2006

The melanocortin agonist, melanotan II, enhances proceptive sexual behaviors in the female rat.

Melanocortins have been reported to play a role in the control of both male and female sexual behavior. The present study examined the effects of melanotan-II (MT-II), a cyclic peptide analogue of alpha-melanocyte stimulating hormone on appetitive and consummatory aspects of female sexual behavior, including aspects of sexual proceptivity (solicitations, hops and darts, ear wiggling, pacing) and receptivity (lordosis). One group of ovariectomized Long-Evans rats (n=7) was primed subcutaneously with estradiol benzoate (EB) and progesterone (P) (10 microg and 500 microg respectively) and another group (n=7) with EB (10 microg) and oil (EB alone). Paced mating tests were performed with sexually experienced males in unilevel chambers, which were bisected by a Plexiglas divider containing three holes, through which only the female could pass. MT-II (1 and 3 mg/kg) or saline was injected intravenously 10 min before each 30-min paced mating test. Each female received the 3 treatments. In females primed with EB+P both doses of MT-II increased the number of hops and darts and ear wiggling significantly, but did not alter pacing or lordosis. With EB alone, no effect of MT-II was observed on any of the parameters measured. These results suggest that P can interact with MT-II to increase proceptive behaviors. Because hops and darts are essentially solicitations, made in close proximity to the male, that indicate a desire on the part of females to receive mounts and intromissions, these data suggest that activation of melanocortin receptors may represent a promising mode of action for the treatment of women with hypoactive sexual desire.

Animals↗
PubMed2006

Effects of pelvic, pudendal, or hypogastric nerve cuts on Fos induction in the rat brain following vaginocervical stimulation.

In the female rat, genitosensory input is conveyed to the central nervous system predominantly through the pelvic, pudendal, and hypogastric nerves. The present study examined the relative contribution of those three nerves in the expression of Fos immunoreactivity within brain regions previously shown to be activated by vaginocervical stimulation (VCS). Bilateral transection of those nerves, or sham neurectomy, was conducted in separate groups of ovariectomized, sexually-experienced females. After recovery, females were primed with estrogen and progesterone and given either 50 manual VCSs with a lubricated glass rod over the course of 1 h. VCS increased the number of neurons expressing Fos immunoreactivity in the medial preoptic area, lateral septum, bed nucleus of the stria terminalis, ventromedial hypothalamus, and medial amygdala of sham neurectomized females. Transection of the pelvic nerve reduced Fos immunoreactivity in the medial preoptic area, bed nucleus of the stria terminalis, ventromedial hypothalamus, and medial amygdala, whereas transection of the pudendal nerve had no effect. In contrast, transection of the hypogastric nerve increased Fos immunoreactivity in the medial preoptic area and lateral septum, whereas transaction of the pelvic nerve increased Fos immunoreactivity in the lateral septum, following VCS. All females given VCS, except those with pelvic neurectomy, displayed a characteristic immobility during each application. These data confirm that the pelvic nerve is largely responsible for the neural and behavioral effects of VCS, and support a separate function for the hypogastric nerve.

Analysis of Variance↗
PubMed2006

Conditioned partner preference in female rats for strain of male.

Female rats show conditioned place preference following paced copulation, and we have recently demonstrated that pairing almond odor with paced copulation induces a conditioned partner preference for almond-scented males. The present study examined whether cues of two different strains of male (albino and pigmented) induce a conditioned partner preference for the strain of male associated with paced copulation. Ovariectomized, hormone-primed Wistar (W) or Long-Evans (LE) female rats received 10 conditioning trials at 4-day intervals. In the Wistar-pacing group females copulated with W males in a chamber bisected by a 4-hole partition that only the female could pass through. Four days later, they copulated with LE males without the partition. The Long-Evans-pacing group received the opposite association. In the final preference test all females chose freely between two males tethered in opposite corners of an open field, one W and one LE. Regardless the strain of male, females displayed more solicitations toward the pacing-related male, and most of the females received their first ejaculation from that male. The preference was facilitated if the pacing-related male was of the same strain as the female. These results suggest that female rats have an unconditioned preference for males of the same strain, but this preference can be switched towards males of a different strain if that male is associated with the sexual reward induced by paced copulation.

Animals↗
PubMed2006

Role of glutamate receptors in the ventromedial hypothalamus in the regulation of female rat sexual behaviors I. Behavioral effects of glutamate and its selective receptor agonists AMPA, NMDA and kainate.

Bilateral infusions of glutamate or kainate to the ventromedial hypothalamus (VMH) have been shown previously to produce a rapid inhibition of lordosis in estrogen-primed female rats induced by manual flank stimulation. The present study examined whether glutamate or selective ionotrophic glutamate receptor agonists can disrupt appetitive and consummatory sexual behaviors following bilateral infusions to the VMH of females during copulation with male rats. Ovariectomized, sexually experienced female rats were implanted bilaterally with guide cannulae aimed at the ventrolateral VMH. After recovery from surgery, females were primed with estradiol benzoate and progesterone and infused with different doses of glutamate, AMPA, NMDA or kainate (n=9-10 in each dose group) 3 min prior to a test with sexually vigorous males in bilevel chambers. Glutamate infusions decreased the display of hops and darts and produced a trend toward decreased lordosis. AMPA infusions decreased the display of solicitations, hops and darts, and lordosis. NMDA infusions decreased lordosis and increased defensive behaviors and pacing. Kainate infusions decreased solicitations, hops and darts, and lordosis, and increased defensive behaviors and pacing. These data indicate that the activation of glutamate receptors in the VMH is inhibitory for both appetitive and consummatory aspects of sexual behavior in the female rat.

Animals↗
PubMed2006

Role of glutamate receptors in the ventromedial hypothalamus in the regulation of female rat sexual behaviors. II. Behavioral effects of selective glutamate receptor antagonists AP-5, CNQX, and DNQX.

Bilateral infusions of glutamate or its selective ionotrophic receptor agonists to the ventromedial hypothalamus (VMH) produce a rapid inhibition of both appetitive and consummatory sexual behavior in hormone-primed female rats. The present study examined whether infusion of selective ionotrophic glutamate receptor antagonists to the VMH can facilitate female sexual behavior in females treated with estradiol benzoate (EB) and progesterone (P), or EB alone. Ovariectomized, sexually experienced female rats were implanted bilaterally with guide cannulae aimed at the ventrolateral VMH. After recovery from surgery, females were primed either with EB+P or EB alone, and infused with saline, or one of two doses each of AP-5 (to target NMDA receptors), CNQX, or DNQX (to target AMPA/kainate receptors), immediately before tests with sexually vigorous male rats in bilevel chambers. In general, the drug infusions had a more powerful effect in females primed with EB alone compared to females primed with EB+P. AP-5 increased lordosis in females primed with EB alone. CNQX had a similar facilitative effect on lordosis, and also increased solicitations. DNQX increased solicitations in both hormone-priming conditions, increased lordosis quotients and magnitudes, and decreased pacing and defensive responses in the EB-alone condition. These results indicate that antagonism of glutamate receptors in the VMH resembles the effect of P, and that the addition of P to an EB baseline eliminates most of the effects of glutamate receptor antagonists. These data support the notion that glutamate receptors in the VMH contribute a strong inhibitory influence in the control of female sexual behavior.

2-Amino-5-phosphonovalerate↗
PubMed2006

Sensory mediation of female-male mounting in the rat: II. Role of tactile and conspecific cues.

Although previous research has shown that olfactory cues mediate female-male mounting (FMM) in the rat, the role of other sensory modalities on FMM has not been investigated. The present study examined the display of female mounting of castrated male rats in bilevel chambers following different tactile or locomotor activity manipulations. Female rats (N = 40) were ovariectomized (OVX), primed with estrogen (E) and progesterone (P), and given either vaginocervical stimulation (VCS), flank/perineum stimulation (FPS), combined VCS and FPS, or general handling, immediately before each test with a castrated male rat for five trials. Compared to handling, the FPS females showed an increase in FMM behavior, whereas females given VCS, or combined VCS and FPS, showed a decrease in FMM behavior. A second experiment examined the effect of a 15-min delay between stimulation and testing using identical experimental and control conditions. There were no significant differences in the amount of FMM behavior between these groups. Finally, OVX rats primed with E and P were tested with castrated males that had been given injections of a ketamine/xylazine anesthetic mixture, saline, or amphetamine, to induce three levels of conspecific locomotor activity: none, moderate, or high, respectively. A positive linear relationship was found between male activity level and FMM. These data indicate that both tactile cues and cues associated with locomotor activity of the stimulus male modulate FMM.

Amphetamine↗
PubMed2006

Sensory mediation of female-male mounting in the rat: I. Role of olfactory cues.

Previous research has shown that olfactory cues mediate the mounting of female rats by male or other female rats. The present study examined whether olfactory cues might mediate the mounting of castrated, sexually inactive male rats by sexually receptive female rats (female-male mounting, or FMM). The effects of olfactory impairment, created by either olfactory bulbectomy (OBx) or olfactory occlusion (OOc), on FMM were investigated. Ovariectomized, hormone-primed female rats were given either OBx (OBx+) or sham (OBx-) surgeries. OBx+ females did not engage in any FMM after surgery, whereas sham-operated females continued to mount at baseline levels. This effect was replicated using OOc, a reversible form of olfactory impairment that involves the cannulation of the nasal cavity with a flexible tube. Females were either given the OOc surgery (OOc+), the OOc surgery with the tube removed immediately after placement (OOc-), or sham surgery in which the animal was only anesthetisized. OOc+ females, like OBx+ females, did not display FMM, whereas both control groups continued to mount at baseline levels. The effect of prior experience with FMM was also examined. Females were given either 0 or 5 encounters with castrated males prior to OBx+, OOc+, or OOc- surgeries. OBx+ and OOc+ females did not mount, regardless of prior mounting experience. These data indicate that the olfactory sense is a prime mediator of FMM, and that prior mounting experience does not offset the disruption of FMM caused by the elimination of olfactory cues.

Analysis of Variance↗
PubMed2005

Hormonal and experiential control of female-male mounting in the female rat.

Mounting behavior in the female rat has been studied extensively in same-sex interactions, but not in the heterosexual dyad. The present study examined the display of female mounting of castrated noncopulating male rats (FMM). Ovariectomized (OVX) sexually naive female rats (N = 80) were given either estrogen (E) + progesterone (P), E + oil (O), P + O, or O + O treatment for five tests with castrated male rats. FMMs were observed in both the E + P and E + O females. The influence of the ovarian cycle on FMM was also investigated. Vaginal smears from sexually naive females (N = 16) were taken daily for 12 days immediately after testing with castrated males. FMM frequency was greatest during Proestrus. Finally, OVX females (N = 30) treated with E + P were given either 0, 1, 10 multi-ejaculatory heterosexual experiences with intact, sexually experienced males, prior to tests with intact, copulating or castrated, noncopulating males for five tests. Sexually naive females displayed a greater number of mounts relative to the sexually experienced females when tested with castrated, noncopulating males. In contrast, very few FMMs were observed in females of any group tested with intact, copulating males. These data suggest that FMM occurs naturally in rats as a "super-solicitational" behavior that is modified by hormone treatment and prior heterosexual experience.

Animals↗
PubMed2005

A sexually dimorphic hypothalamic nucleus in a macaque species with frequent female-female mounting and same-sex sexual partner preference.

In some captive and free-ranging populations, unmanipulated female Japanese macaques (Macaca fuscata) routinely court, mount (with pelvic thrusting), compete for, and even prefer, on occasion, certain female sexual partners over certain males. The goal of this study was to determine if the cytoarchitecture of the dorsocentral portion of the anterior hypothalamic nucleus (AHdc), was male-typical in female Japanese macaques drawn from one such population. The AHdc is located in the medial preoptic anterior hypothalamus (MPO-AH), a region of the brain that is known to regulate sexual behaviour in primates. Despite their potential for male-typical sexual behaviour and sexual partner preference, our female subjects did not possess male-typical AHdc. The AHdc was significantly larger in males than it was in females, a difference that could be attributed to the significantly larger number of neurons in the male AHdc compared to that of the females. The AHdc of female Japanese macaques were no more male-typical in size than those of female rhesus macaques, a closely related sister species in which females rarely exhibit male-typical sexual behaviour. Although the AHdc may be involved in the regulation of sexual behaviour, this study indicates that a male-typical AHdc is not a prerequisite for the expression of male-typical sexual behaviour and sexual partner preference in Japanese macaques. This study is the first to examine the relationship between sex-atypical sexual activity and the cytoarchitecture of a hypothalamic nucleus in hormonally unmanipulated females.

Animals↗
PubMed2005

Olfactory conditioned partner preference in the female rat.

Paced copulation induces conditioned place preference in female rats. The authors examined whether associating almond-scented males with paced copulation induces conditioned partner preference. The paired group received 4 paced copulations with almond-scented males and 4 nonpaced copulations with unscented males sequentially at 4-day intervals. The unpaired group received the opposite order of association, whereas the randomly paired group received random associations. A 4th group received a single pairing. On the final test, females were placed into an open field with 2 males, 1 scented and 1 unscented. Females in the paired group solicited the scented male more frequently, and most chose the scented male for their 1st ejaculation. Thus, an odor paired with paced copulation elicits conditioned partner preference in female rats.

Analysis of Variance↗
PubMed2004

Selective facilitation of sexual solicitation in the female rat by a melanocortin receptor agonist.

Disorders of sexual desire affect an estimated 30% of women in North America and Europe, with etiologies based on interpersonal, personal, and physiological factors. There are currently no pharmacological agents approved for use in the treatment of female sexual dysfunction. This is due, in part, to a focus on the effects of experimental drugs on reflexive components of sexual behavior, such as lordosis, in animal models. Here we report that PT-141, a peptide analogue of alpha-melanocyte-stimulating hormone that binds to central melanocortin receptors, selectively stimulates solicitational behaviors in the female rat. This occurs without affecting lordosis, pacing, or other sexual behaviors. PT-141 did not cause generalized motor activation, nor did it affect the perception of sexual reward. A selective pharmacological effect on appetitive sexual behavior in female rats has not been reported previously, and indicates that central melanocortin systems are important in the regulation of female sexual desire. Accordingly, PT-141 may be the first identified pharmacological agent with the capability to treat female sexual desire disorders.

Animals↗
PubMed2004

Timing between ejaculations changes paternity success.

It is believed that when two male rats copulate with a single female, the last one that ejaculates fathers significantly more pups than the first one. To determine the effects of order and elapsed time between two males copulating with the same female, albino Wistar (W) and pigmented Long-Evans (LE) male rats copulated with a W female. Paternity was confirmed by the pups' pigmentation. Three groups were made according to the elapsed time between the first male's ejaculation and the placement of the female with the second male; T0 (0-min group); T5 (5-min group); and T10 (10-min group). Male order was counterbalanced in each group. The results showed that the second male had the advantage in T0, but the first males had the advantage in T5 and T10. These data indicate that in a two-male situation, the advantage in paternity for a second male occurs only during copulations following the first few minutes of a first male's ejaculation. After 5 min, a second male has no advantage in fathering pups.

Animals↗
PubMed2004

Opposing roles of the nucleus accumbens and anterior lateral hypothalamic area in the control of sexual behaviour in the male rat.

Opposing roles have been implicated for the nucleus accumbens (NAc) and anterior portion of the lateral hypothalamic area (aLHA) in the regulation of sexual behaviour in male rats based on in vivo neurochemical correlates. The present study provides functional evidence supporting this hypothesis by examining the effects of lesions to these structures on copulation, noncontact erection and receptive female preference. Sexually naïve male Long-Evans rats received either bilateral 1.0- micro L injections of NMDA (10 micro g/ micro L/side) or vehicle (shams) into either the aLHA or the NAc. During repeated tests of copulation most of the sham-lesioned males, but few of the aLHA-lesioned and NAc-lesioned males, copulated to ejaculation. Most of the NAc-lesioned males also failed to intromit, whereas the majority of the aLHA-lesioned males intromitted repeatedly. During exposure to an inaccessible receptive female behind a wire-mesh screen, aLHA-lesioned males displayed facilitation of noncontact erections, whereas NAc-lesioned males displayed impaired noncontact erections. Conversely, during simultaneous exposure to inaccessible receptive and nonreceptive females in different compartments, all males spent more time in the proximity of the receptive female. These findings indicate that the aLHA plays an inhibitory role in the regulation of sexual arousal and an excitatory role in the regulation of ejaculation. Conversely, the NAc plays an excitatory role in the regulation in sexual arousal.

Animals↗
PubMed2003

What can animal models tell us about human sexual response?

In all species, sexual behavior is directed by a complex interplay between steroid hormone actions in the brain that give rise to sexual arousability and experience with sexual reward that gives rise to expectations of competent sexual activity, including sexual arousal, desire, and performance. Sexual experience allows animals to form instrumental and Pavlovian associations that predict sexual outcome and thereby directs the strength of sexual responding. Although the study of animal sexual behavior by neuroendocrinologists has traditionally been concerned with mechanisms of copulatory responding, more recent use of conditioning and preference paradigms, and a focus on environmental circumstances and experience, has revealed behaviors and processes that resemble human sexual responses. In this paper, we review behavioral paradigms used with rodents and other species that are analogous or homologous to human sexual arousal, desire, reward, and inhibition. The extent to which these behavioral paradigms offer predictive validity and practicality as preclinical tools and models is discussed. Identification of common neurochemical and neuroanatomical substrates of sexual responding between animals and humans suggests that the evolution of sexual behavior has been highly conserved and indicates that animal models of human sexual response can be used successfully as preclinical tools.

Animals↗