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J G Pfaus

Publications and source records attributed to J G Pfaus.

At least 37 records · Page 2Linked to original sources

Sexual stimulation induces Fos immunoreactivity within GnRH neurons of the female rat preoptic area: interaction with steroid hormones.

We have shown previously that sexual stimulation (copulation with intromission or vaginocervical stimulation) induces c-fos mRNA and Fos-like immunoreactivity (IR) within estrogen-concentrating and nonconcentrating regions of the female rat forebrain, including regions that contain gonadotropin-releasing hormone (GnRH) neurons in septum and anterior preoptic area. The overall induction of Fos-like IR within these regions was specific to afferent sensory stimulation and did not require treatment with estrogen and progesterone. Because vaginocervical stimulation facilitates lordosis and increases the release of luteinizing hormone, the present study examined whether hormone treatment that promotes sexual receptivity, with or without sexual stimulation, increases Fos-like IR specifically within GnRH-containing neurons. Sexually experienced ovariectomized rats were administered estradiol benzoate (10 micrograms) 48 h and progesterone (500 micrograms) 4 h before either 1 h of paced copulation with a sexually vigorous male, 50 vaginocervical stimulations with a glass rod distributed over 1 h, or no stimulation. Control rats received injections of the oil vehicle. Fos-like IR was found within a significant number of GnRH-positive neurons in the anterior preoptic area caudal to the organum vasculosum following copulation with intromission or vaginocervical stimulation as compared with no stimulation. Although few GnRH cells coexpressed Fos following hormone treatment alone, this treatment enhanced the number of GnRH neurons that coexpressed Fos following vaginocervical stimulation as compared with the effect of vaginocervical stimulation in oil-treated rats. Together, these data indicate that estrogen and progesterone can augment the responsiveness of certain GnRH neurons to vaginocervical stimulation, consistent with the effects of sexual activity on GnRH release.

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Sexual stimulation activates c-fos within estrogen-concentrating regions of the female rat forebrain.

Regions of the brain that concentrate estrogen and progesterone are thought to regulate female sexual behavior by altering gene expression and neural sensitivity to afferent stimulation. We used immunocytochemistry and in situ hybridization to examine c-fos gene expression within estrogen-concentrating regions of the forebrain following various types of sexual stimulation with or without hormone treatment. Ovariectomized rats received injections of estradiol benzoate 48 h and progesterone 4 h before testing. Control rats that had been ovariectomized at least 5 months before testing did not receive hormone treatment. Rats were then either placed into bilevel testing chambers with sexually vigorous males, received manual stimulation of the flanks, received vaginocervical stimulation with a glass rod, or were left in their home cages. Copulation with intromission and ejaculation in hormone-treated rats, or stimulation of the vaginal cervix in both hormone-treated and control rats, produced a dramatic induction of c-fos mRNA and Fos-like immunoreactivity in estrogen-concentrating regions, such as the lateral septum, medial preoptic area, bed nucleus of the stria terminalis, paraventricular nucleus of the hypothalamus, ventromedial hypothalamus, lateral habenula, and medial amygdala, in addition to regions that do not readily concentrate estrogen, such as the neocortex, thalamus, and striatum. Mechanical stimulation of the flanks produced a smaller induction of Fos in these rats, whereas hormone treatment alone had no effect. These data demonstrate that afferent sensory stimulation, but not estrogen or progesterone, regulates c-fos gene expression within different estrogen-concentrating and non-concentrating regions of the female rat forebrain.

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Dopamine transmission increases in the nucleus accumbens of male rats during their first exposure to sexually receptive female rats.

In vivo microdialysis was used to monitor extracellular concentrations of dopamine (DA), and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the nucleus accumbens of sexually naive male rats during their first exposure to sexually receptive or nonreceptive females. DA, DOPAC, and HVA increased progressively and significantly in males that copulated to ejaculation with receptive females. In contrast, DA, DOPAC, and HVA did not increase significantly in males exposed to non-receptive females, despite several attempts by these males to mount the non-receptive females. These results indicate that DA is released unconditionally in the nucleus accumbens of male rats by exposure to sexually receptive female rats, and that copulation with intromission, but not mounting alone, leads to further increases in DA release.

3,4-Dihydroxyphenylacetic Acid↗

Induction of FOS immunoreactivity in oxytocin neurons after sexual activity in female rats.

Several lines of evidence suggest that centrally released oxytocin (OT) may act in the hypothalamic ventromedial nucleus (VMN) to facilitate sexual behavior in female rats primed with estradiol and progesterone. The present experiment used a marker of neuronal activation, expression of the transcription factor FOS, to locate OT neurons activated during sexual behavior. Sexual behavior significantly increased the percentage of OT neurons in the hypothalamic paraventricular nucleus (PVN) expressing FOS in rats treated with estradiol and progesterone, compared to hormone-treated, nonmated controls. The OT neurons colabelled with FOS immunoreactivity were found in regions of the PVN, but not in the supraoptic nucleus. As reported by others, FOS expression also was induced in the preoptic area and the VMN. Taken together with other evidence, the results are consistent with the hypothesis that endogenous OT is involved in female sexual behavior, and suggest that the source of oxytocinergic innervation to the oxytocin receptors in the VMN may be neurons in the PVN. Interestingly, FOS expression in the VMN occurred in cells in the vicinity of OT fibers.

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Gene memory in neuroendocrine and behavioural systems.

Several examples of sex steroid hormone actions on rat brain and behaviour show that initial hormone exposures may be followed by enduring neuronal alterations, apparent long after the hormone itself has disappeared. Precedents from non-neuronal systems led to the concept of 'gene memory'. We are studying genomic structural alterations in rat hypothalamic neurons to account for these effects. The preproenkephalin gene is turned on by oestradiol in rat brain neurons in a tissue-specific and genetic sex-specific manner. Levels of preproenkephalin mRNA in the ventromedial hypothalamus correlate tightly with oestradiol-dependent reproductive behaviour. Our results indicate a tissue-specific pattern of DNA methylation in the enkephalin promoter. Putative binding sites for several transcription factors have been described in the preproenkephalin gene promoter; a role for some of these factors in regulating expression of the gene has been demonstrated.

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Mu-, delta-, and kappa-opioid receptor agonists selectively modulate sexual behaviors in the female rat: differential dependence on progesterone.

Previous studies suggested that opioid receptor agonists infused into the lateral ventricles can inhibit (through mu receptors) or facilitate (through delta receptors) the lordosis behavior of ovariectomized (OVX) rats treated with estrogen and a low dose of progesterone. The present study investigated the behavioral and hormonal specificity of those effects using more selective opioid receptor agonists. Sexually experienced OVX rats were implanted stereotaxically with guide cannulae aimed at the right lateral ventricle. One group of rats was treated with estradiol benzoate (EB, 10 micrograms) 48 hr and progesterone (P, 250 micrograms) 4 hr before testing, whereas the other group was treated with EB alone. Rats were infused with different doses of the selective mu-receptor agonist DAMGO, the selective delta-receptor agonist DPDPE, or the selective kappa-receptor agonist U50-488. The females were placed with a sexually vigorous male in a bilevel chamber (Mendelson and Gorzalka, 1987) for three tests of sexual behavior, beginning 15, 30, and 60 min after each infusion. DAMGO reduced lordosis quotients and magnitudes significantly in rats treated with EB and P, but not in rats treated with EB alone. In contrast, DPDPE and U50-488H increased lordosis quotients and magnitudes significantly in both steroid-treatment groups. Surprisingly, measures of proceptivity, rejection responses, and level changes were not affected significantly by mu or kappa agonists, although proceptivity and rejection responses were affected by DPDPE treatment. These results suggest that the effects of lateral ventricular infusions of opioid receptor agonists on the sexual behavior of female rats are relatively specific to lordosis behavior. Moreover, the facilitation of lordosis behavior by delta- or kappa-receptor agonists is independent of progesterone treatment, whereas the inhibitory effect of mu-receptor agonists on lordosis behavior may require the presence of progesterone.

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Contingent tolerance to the disruptive effects of alcohol on the copulatory behavior of male rats.

Sexually active male rats received five 30-min copulation tests with sexually receptive females, one every 4 days. One group of rats received alcohol (1 g/kg, IP) 45 min before, and an equivalent volume of saline 45 min after, each test; a second group received saline before and alcohol after each test; and a third, control group received saline both before and after. Four days after the last of the five tolerance-development trials, each rat received an injection of alcohol (1 g/kg, IP) 45 min before a copulation test so that the development of tolerance in the three groups could be compared. Tolerance to the disruptive effects of alcohol on mount, intromission, and ejaculation latencies, and on the duration of the postejaculatory interval was found to be significantly greater in the rats injected with alcohol before each copulation test than it was in the rats in the other two groups. These results constitute the first experimental evidence that tolerance develops to the disruptive effects of alcohol on male sexual behavior, and they support the theory that tolerance is an adaptive response to the disruptive effects of drugs on concurrent patterns of neural activity, rather than to drug exposure per se.

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Dopamine functions in appetitive and defensive behaviours.

The data reviewed here are compatible with the hypothesis that telencephalic dopamine activity is elicited by motivationally significant stimuli which in turn creates a neural state in which animals are more prepared to respond to significant stimuli in the environment. This analysis may be viewed as extensions of both the sensorimotor hypothesis, which depicts dopamine as potentiating the ability of stimuli to elicit responses (Clody and Carlton, 1980; Marshall et al., 1974; White, 1986) and of the incentive motivational hypothesis, which emphasizes the importance of dopamine in responding to stimuli that serve as signals of biologically significant events (Blackburn et al., 1989a; Crow, 1973; Mogenson and Phillips, 1976). In addition, we have sought to emphasize that not all responses are equally dependent upon the integrity of forebrain dopamine activity. Some responses, such as ingestion of standard foods by hungry animals, copulation, and escape, are relatively impervious to dopamine disruption. Further, once other behaviours, such as avoidance or appetitive operant responses, have been acquired, they can be maintained at an initially high rate despite perturbation of dopamine systems, although performance deteriorates with repeated testing. This analysis has emerged from the joint consideration of how both appetitive and defensive behaviours are influenced by dopamine antagonists, along with an examination of dopamine release during sequences of behaviour. The data reviewed suggest that dopamine is involved in fundamental psychological processes through which environmental stimuli come to exert control over certain aspects of behaviour. In the future, as knowledge in this field advances, there will have to be an integration of the literature on dopamine and motivation with the literature on dopamine and motor systems. We expect that dopamine release will be seen as a mechanism by which important environmental cues, of innate or learned significance, lead to a general enhancement of motor skeletal responses directed towards distal cues. We conclude with a caveat: Caution must be exercised when attempting to infer a general role of any neurotransmitter in motivated behaviour based on the study of a limited number of motivational systems. Although neurotransmitter pathways may figure prominently in the control of certain behaviours, it is incorrect to think of neurotransmitters as having a single role in behaviour. However, when comparative analyses reveal a common thread among different motivational systems, as is becoming apparent for the general role of mesotelencephalic dopamine pathways in behaviour, then the goal of generating coherent and comprehensive theory concerning a neurotransmitter's function in behaviour will begin to be realised.(ABSTRACT TRUNCATED AT 400 WORDS)

Aggression↗

Sexual behavior increases dopamine transmission in the nucleus accumbens and striatum of male rats: comparison with novelty and locomotion.

Extracellular concentrations of dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were examined concurrently, using in vivo microdialysis, in the nucleus accumbens and dorsal striatum of sexually active male rats during tests of locomotor activity, exposure to a novel chamber, exposure to sex odors, the presentation of a sexually receptive female, and copulation. DA increased significantly in the nucleus accumbens when the males were presented with a sexually receptive female behind a screen and increased further during copulation. Although DA also increased significantly in the dorsal striatum during copulation, the magnitude of the effect was significantly lower than that observed in the nucleus accumbens. In contrast, forced locomotion on a rotating drum, exposure to a novel chamber, and exposure to sex odors did not increase DA significantly in either region, although both DOPAC and HVA increased significantly in both regions during the locomotion test. These results indicate that novelty or locomotor activity alone cannot account for the increased extracellular DA concentrations observed in the nucleus accumbens of male rats during the presentation of a sexually receptive female behind a screen, nor can they account for the increased DA concentrations observed in both the nucleus accumbens and dorsal striatum of male rats during copulation. The preferential increase in DA transmission in the nucleus accumbens, compared with that in the striatum, suggests that anticipatory and consummatory aspects of sexual activity may belong to a class of naturally occurring events with reward values that are mediated by DA release in the nucleus accumbens.

3,4-Dihydroxyphenylacetic Acid↗

Sexual behavior increases c-fos expression in the forebrain of the male rat.

The ability of a wide variety of pharmacological and physiological stimuli to increase neuronal expression of Fos has led to the suggestion that it might serve as a marker of neuronal activation. Psychomotor stimulants increase the release of dopamine from the terminals of nigrostriatal and mesolimbic neurons and enhance Fos immunoreactivity in the striatum and nucleus accumbens (NAc). Because sexual behavior also increases dopamine release in these and other forebrain regions, the present study examined the effect of copulation on Fos immunoreactivity in the forebrain of intact, sexually active male rats. Sexual behavior produced a striking increase in Fos immunoreactivity in the medial preoptic area (MPOA), NAc, bed nucleus of the stria terminalis and piriform cortex. However, no increase in Fos immunoreactivity was observed in the striatum. These results are consistent with neurochemical, physiological, and behavioral data suggesting that the MPOA and NAc are important substrates of sexual behavior.

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Role of dopamine in anticipatory and consummatory aspects of sexual behavior in the male rat.

The ability of dopamine (DA) receptor antagonists to disrupt anticipatory and consummatory measures of sexual behavior displayed by male rats in bilevel chambers was investigated. In Experiment 1, systemic administration of haloperidol, pimozide, and the D1 antagonist SCH 23390 reduced the number of anticipatory level changes (LC) displayed during a 5-min period before the introduction of a sexually receptive female, increased the mount and intromission latencies (ML and IL), and decreased the number of intromissions before ejaculation (NI) and the total number of ejaculations (NE). The dosages of these drugs required to reduce the LC were lower than those required to increase the ML or IL. Clozapine and the D2 antagonist sulpiride reduced the LC and increased the IL at comparable dosages, although neither drug affected the NI or NE. High dosages of haloperidol, pimozide, and clozapine delayed or abolished level changing and the initiation of copulation. In Experiment 2, bilateral infusions of haloperidol into the nucleus accumbens reduced the LC but did not affect consummatory measures of copulation, whereas bilateral infusions into the dorsal striatum increased the NE. Midline infusions of haloperidol to the medial preoptic area (MPOA) produced nearly all the effects of systemic administration, including a reduced LC, increased ML and IL, a decreased NI, and a decreased NE. These results indicate that both anticipatory and consummatory measures of sexual behavior were disrupted by DA receptor antagonists; however, the measure of anticipatory sexual behavior was more sensitive to disruption than consummatory measures of copulation. DA in the nucleus accumbens and MPOA may be involved in the control of anticipatory sexual behavior, whereas in the MPOA it may also be involved in the initiation of copulation and copulatory rate.

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Sexual behavior enhances central dopamine transmission in the male rat.

Central dopamine transmission was examined in the nucleus accumbens and striatum of sexually experienced male rats during mating behaviour using in vivo brain microdialysis. Dopamine release increased significantly in the nucleus accumbens when males were placed in a novel mating chamber and when a receptive female was introduced behind a screen partitioning this chamber. Subsequently, during copulation dopamine transmission increased sharply, this being followed by a gradual decrease after the female was removed. In contrast, striatal dopamine transmission increased significantly only during copulation. These data provide a neurochemical basis for the well-known interactions between dopaminergic drugs and male sexual behaviour and demonstrate the feasibility of using brain microdialysis to elucidate the neurochemical correlates of motivated behaviour.

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A correlational and factor analysis of anticipatory and consummatory measures of sexual behavior in the male rat.

This study investigated the relationship among measures of anticipatory and consummatory sexual behavior displayed by male rats in the bilevel chambers designed by Mendelson and Gorzalka (1987). Normative data from a standard test of sexual behavior were gathered from 80 intact, sexually experienced male Long-Evans rats and subjected to multiple correlational and factor analyses. The correlational analysis confirmed that several consummatory measures of copulation were related significantly, whereas the anticipatory measure, level changing, was statistically independent of consummatory measures. Factor analysis using orthogonal rotations revealed five factors that accounted for 95% of the intersubject variance for all measures: Copulatory Rate, Initiation, Hit Rate, Mount Count, and Anticipation. These results indicate that at least five conceptual mechanisms are required in any theoretical description of male sexual behavior in the bilevel chamber. In particular, the extraction of separate anticipation and initiation factors indicates that these aspects of male sexual behavior are distinct. The use of bilevel chambers thus may facilitate the identification of potential neurochemical or endocrine mechanisms associated with different aspects of male sexual motivation. In addition, several statistical techniques are discussed with the aim of reducing the elevated experiment-wise error that can occur when related measures of sexual behavior are analyzed independently.

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Differential effects of dopamine receptor antagonists on the sexual behavior of male rats.

In the present experiments, the dose-response effects of the dopamine (DA) receptor antagonists haloperidol, pimozide, clozapine, sulpiride, and metoclopramide, were assessed on patterns of copulatory behavior in intact, sexually active male rats with a high level of sexual experience and performance. The typical neuroleptics haloperidol (0.01-0.5 mg/kg) and pimozide (0.1-5.0 mg/kg) dose-dependently delayed the initiation of copulation and reduced the number of intromissions that preceded ejaculation. The atypical neuroleptics clozapine (0.1-5.0 mg/kg), and sulpiride (0.1-5.0 mg/kg) dose-dependently delayed the initiation of copulation but had no effect on copulatory behavior once it was initiated. In contrast, metoclopramide dose-dependently reduced ejaculation but had no effect on the ability of rats to initiate copulation. These experiments suggest that aspects of copulatory behavior in male rats are affected differently by DA antagonists depending upon their site of action in the brain. Blockade of mesolimbic DA receptors by typical and atypical neuroleptics may delay the initiation of copulation, whereas blockade of mesostriatal DA receptors by typical neuroleptics and metoclopramide may decrease the ejaculation threshold.

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Level searching: a new assay of sexual motivation in the male rat.

Mendelson and Gorzalka recently described a bilevel chamber for the evaluation of rodent sexual behavior. In initial studies it was observed that during 5 min adaptation periods prior to the introduction of a sexually receptive female rat, male rats with prior sexual experience in these chambers would move from level to level in apparent search for the female rat. In Experiment 1, we examined the acquisition of this level searching behavior in male rats. Sexually active male rats were given access to either sexually receptive or nonreceptive female rats following a 5 min period alone in the bilevel chamber. Only male rats that pursued and copulated to ejaculation with sexually receptive females in the bilevel chamber significantly increased the number of their level to level movements in subsequent tests during the 5 min periods prior to the introduction of the female rat. In Experiment 2, male rats that had acquired asymptotic rates of level searching showed a significant attenuation of this behavior when the presentation of a female rat into the chamber was discontinued. These findings lead us to conclude that the increase in level to level movement by the male rat represents a sexually motivated search for the female rat. We suggest that the analysis of the acquisition, maintenance, and extinction of level searching behavior might serve as a simple assay of sexual motivation in the male rat.

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Attenuation of morphine analgesia by the S2 antagonists, pirenperone and ketanserin.

The involvement of serotonin type-2 (S2) receptors in morphine-induced analgesia was assessed by challenging the effect of 10 mg/kg of morphine sulphate (IP) with the S2 receptor blockers, pirenperone and ketanserin. Tail-flick latencies were assessed at 0, 30, 60, 90 and 120 min after injections by measuring the time that it took each rat to remove its tail from a 52 degrees C water bath. Pirenperone, at 0.08, 0.16, and 0.24 mg/kg (SC) attenuated morphine-induced antinociception. In contrast, only the high 10 mg/kg (SC) dose of ketanserin attenuated the effect of morphine. Because pirenperone easily enters the central nervous system whereas ketanserin does not, these results indicate the involvement of central S2 receptors in morphine-induced antinociception. The 10 mg/kg dose of ketanserin, however, did not attenuate the antinociception produced by 100 mg/kg of ketamine. Thus, the antianalgesic effect of S2 receptor blockers may be specific to opioid-mediated analgesia.

Analgesia↗

Cholecystokinin facilitates ejaculation in male rats: blockade with proglumide and apomorphine.

Systemic administration of the active, sulfated form of cholecystokinin-octapeptide (CCK-8S), at a dose known to inhibit dopamine (DA) release, significantly reduced the latency to ejaculate and number of intromissions preceding ejaculation in sexually active male rats. This effect was identical to that reported for low doses of the DA receptor agonist apomorphine, which bind preferentially to presynaptic DA autoreceptors. The facilitatory effect of CCK-8S on ejaculation was blocked by the putative CCK receptor antagonist proglumide and by a presynaptic dose of apomorphine. Blockade of the effect of CCK-8S with a presynaptic dose of apomorphine is consistent with CCK induction of depolarization block in DA neurons. These data suggest that CCK-8S and apomorphine may reduce the ejaculation threshold in sexually active male rats by inhibition of DA release via two different mechanisms of action.

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