Prenatal !b-endorphin can modulate some aspects of sexual differentiation in rats.

Sexually dimorphic traits were studied in offspring of rats injected with 33 μg rat β-endorphin (β-END) 3 times daily from Day 14 to Day 21 of pregnancy. β-END males had shorter neonatal anogenital distances than did controls and were more likely to show the female lordosis pattern as adults, but they did not differ in male copulatory behavior. When given a choice between spending time with an estrous female or a male, β-END males showed a lower preference for the female than did control males. The number and somal size of neurons in the bulbocavernosus and dorsolateral nucleus of the lumbar spinal cord were unaffected by drug exposure. Elevated β-END during fetal ontogeny apparently alters the differentiation of some, but not all, sexually dimorphic traits. The data suggest that endogenous opioids may contribute to the etiology of the prenatal stress syndrome. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sexual reinforcement is blocked by infusion of naloxone into the medial preoptic area.

Determined whether infusions of naloxone into specific brain sites can block sexual reinforcement as evaluated with the conditioned place preference procedure. Methylnaloxonium (5 μg/cannula) was infused bilaterally either into the medial preoptic area (MPOA) or into the nucleus accumbens (NAC) of sexually experienced male rats. The MPOA was chosen because it is important for sexual behavior, and several opioid peptides have been shown to modify sexual behavior when infused there. The NAC appears to be a critical structure for drug-induced reward. Methylnaloxonium blocked place preference produced by ejaculation after infusion into the MPOA without affecting sexual behavior. Infusion of the antagonist into the NAC did not reduce the reinforcing properties of ejaculation. Data suggest that the MPOA may be a site where sexual reward is produced. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

MPOA lesions affect female pacing of copulation in rats.

This study examined the effects of electrolytic and ibotenic acid (IA) lesions of the medial preoptic area (MPOA) on the temporal pattern of female sexual behavior in the laboratory rat. Both electrolytic and IA MPOA lesions significantly increased the female's latency to return to the male after an intromission or an ejaculation, thereby decreasing the percentage of time spent with a male. Both types of MPOA lesions significantly increased the percentage of times the female left the male's chamber following intromissions. These results demonstrate that neurons in the MPOA regulate the female's temporal copulatory behavior, and the authors suggest that they do so by virtue of their response to vaginocervical stimulation. Studies of female pacing draw attention to parallels between male and female sexual behaviors, including the possibility that they are regulated by similar neural substrates in the MPOA. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Additive wake-promoting actions of medial basal forebrain noradrenergic α1- and β-receptor stimulation.

The locus coeruleus-noradrenergic system exerts an activating influence on forebrain neuronal and behavioral activity states, in part through the actions of noradrenergic β-receptors in the medial septal (MS) and medial preoptic (MPOA) areas. MPOA α1-receptors exert similar wake-promoting actions. The current study examines the influence of α1-receptors located within MS on sleep-wake state. In addition, the extent to which α1- and β-receptors located within MS and MPOA interact in the modulation of behavioral state was investigated by examining the effects of individual or combined infusion of α1- and β-agonists into these regions. Results show that al-receptors located within MS exert wake-promoting actions. Within both MS and MPOA, additive wake-promoting actions were observed with α1- and β-receptor stimulation, the sum of which contributes to the overall arousal state of the animal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mating activates NMDA receptors in the medial preoptic area of male rats.

Studies have emphasized the role of the medial preoptic area (MPOA) as an important site for the regulation of male sexual behavior. Indeed, ablations of the MPOA impair sexual behavior, whereas stimulation of the MPOA enhances behavior. Furthermore, neural activity in the MPOA increases with mating. The current study tested the hypothesis that activation of N-methyl-D-aspartate (NMDA) receptors occurs in MPOA neurons and is essential for the expression of male sexual behavior in rats. Results indicate that nearly all MPOA neurons that expressed Fos following mating also contained the NR1 subunit of NMDA receptors. Furthermore, mating increased phosphorylation, thus activation, of NR1 in the MPOA. Additionally, blocking NMDA receptors significantly decreased mating-induced Fos expression and mating-induced phosphorylation of NMDA receptors and impaired male sexual behavior. These results provide evidence that mating activates NMDA receptors in the MPOA and that this activation is important for the expression of male sexual behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Serotonin impairs copulation and attenuates ejaculation-induced glutamate activity in the medial preoptic area.

The medial preoptic area (MPOA) is critical for male sexual behavior. Glutamate is released in the MPOA of male rats during copulation, and increasing glutamate levels by reverse dialysis of glutamate uptake inhibitors facilitates mating. Conversely, increased release of serotonin (5-HT) inhibits sexual behavior. In both rats and men, selective serotonin reuptake inhibitors (SSRIs) impair erection, ejaculation, and libido. Here we reverse-dialyzed 5-HT through concentric microdialysis probes in the MPOA of male rats; concurrently we collected 2-min samples for analysis of glutamate and measured sexual behavior. Sexual activity, and especially ejaculation, increased levels of glutamate in the MPOA. However, reverse dialysis of 5-HT into the MPOA impaired ejaculatory ability and attenuated glutamate release. Implications of these results for impairment of sexual behavior that results from administration of SSRIs are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Wake-Promoting Actions of Medial Basal Forebrain β? Receptor Stimulation.

The locus coeruleus-noradrenergic system exerts an activating influence on forebrain neuronal and behavioral activity states, in part, through the actions of noradrenergic β receptors located within the medial septal (MS) and medial preoptic (MPOA) areas. The current study examined the extent to which β? receptors located within these medial basal forebrain regions modulate behavioral state. In this study, the sleep-wake effects of microinfusion of the β? agonist, clenbuterol, into the MS and MPOA were examined. Clenbuterol infusion into both MS and MPOA elicited a dose-dependent increase in time spent awake. These observations indicate that medial basal forebrain β? receptors participate in the noradrenergic-dependent modulation of behavioral state. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of lesion location within the medial preoptic-anterior hypothalamic continuum on maternal and male sexual behaviors in female rats.

Lesions of the medial preoptic-anterior hypothalamic continuum (MPOA-AH) disrupt both maternal behavior and male sexual behavior in the rat. To test the hypothesis that the 2 behaviors involve different neural systems in the MPOA-AH, small bilateral lesions were made in different anterior-posterior locations in the MPOA-AH of 41 maternal-sensitized Charles River female rats treated with testosterone propionate (.5 mg/day, sc), and the effects of these lesions on maternal and male sexual behaviors were assessed. Lesions centering in the MPOA disrupted maternal behavior (pup retrieval, nest building, and nursing), with anterior MPOA lesions being more effective (on pup retrieval and nest building) than posterior MPOA lesions. Lesions centering in the AH had little or no effect on maternal behavior. By contrast, male sexual behavior (mounting) was strongly disrupted by lesions in either the MPOA or the AH, with lesions in the rostral AH being most effective. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The medial and lateral cell groups of the sexually dimorphic area of the gerbil hypothalamus are essential for male sex behavior and act via separate pathways

Male reptiles, birds and mammals do not copulate if the medial preoptic area (MPOA) is destroyed but the MPOA cell groups necessary for male sexual behavior were not known. Here, two cell groups essential for copulation are identified in the sexually dimorphic area (SDA) of the gerbil (Meriones unguiculatus) MPOA. Bilateral cell-body lesions of either the medial or lateral SDA eliminated mating in sexually experienced male gerbils given testosterone. Nearby MPOA lesions did not. The medial and lateral SDA affect sex behavior via separate pathways since lesioning the medial SDA on one side of the brain and the lateral SDA on the other did not stop sexual behavior.     

Dopamine release in the medial preoptic area of female rats in response to hormonal manipulation and sexual activity.

Dopamine (DA) is responsive to hormonal manipulations and has been implicated in the regulation of female rat sexual behavior. In the present studies, extracellular DA levels were assessed in the medial preoptic area (MPOA) of ovariectomized female rats in response to exogenous ovarian hormones and during sexual activity. In female rats primed with a low dose of estradiol benzoate (2 μg), but not with a higher dose (20 μg), a 500-μg progesterone injection increased extracellular DA and facilitated copulatory behavior. Extracellular DA levels in the MPOA were further augmented during sexual interactions with a male rat in a nonpacing copulatory chamber by either perineal or vaginal stimulation. However, in a pacing chamber, DA efflux did not increase, although the metabolites rose significantly during copulation. Together, these findings suggest that extracellular DA in the MPOA responds to the hormonal state of the female rat and may contribute to her expression of sexual behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Roles of gonadotropins and releasing hormones in hypothalamic control of lordotic behavior in ovariectomized, estrogen-primed rats.

Intrahypothalamic effects of gonadotropins (luteinizing hormone and follicle-stimulating hormone, LH and FSH, respectively), thyrotropin-releasing hormone (TRH), and luteinizing-hormone-releasing hormone (LRH) on lordotic behavior were evaluated in 63 Wistar ovariectomized (OVX) rats maintained at different receptivity levels. Under low receptivity, in which LRH has been shown to enhance mating behavior, medial preoptic area (MPOA) infusions of LH caused significant depressions in the lordotic response, whereas LH infusions into arcuate ventromedial area (ARC-VM) had no significant effect. FSH infusions into either area did not alter the response. In Exp II, in which OVX Ss were primed with higher doses of estrone to maintain high preinfusion receptivity, MPOA or ARC-VM infusions of either LH or TRH depressed lordotic behavior significantly, whereas neither LRH nor FSH inhibited the response. Exp III evaluated the effects of LH, FSH, and TRH on LRH-facilitated mating behavior with 50 Sprague-Dawley male rats. Infusions of LRH into either MPOA or ARC-VM significantly enhanced mating behavior, whereas addition of TRH or LH to the LRH infusates abolished this response. The antagonistic effects of LH and TRH on LRH-facilitated mating were correlated with previous observations of antagonistic effects on hypothalamic unit activity and monoamine metabolism. The antagonistic interrelation between LRH and LH may represent a mechanism for activation and coordination of sexual receptivity with ovulation. (55 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sexual experience increases nitric oxide synthase in the medial preoptic area of male rats.

Nitric oxide in the medial preoptic area (MPOA) is important for the expression and sensitization of male sexual behavior. In this article, the authors report that repeated sexual experience (mating for 2 hr on each of 3 days) increased levels of nitric oxide synthase (NOS) in the MPOA of male rats, regardless of whether they mated on the day they were given an overdose of sodium phenobarbital. This effect resulted from the previous experience and not acute mating, as NOS was not increased 2 hr after the first mating in previously naive males. Experience-induced increases in NOS in the MPOA may be one mechanism through which sexual experience facilitates sexual behavior in male rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of morphiceptin in the medial preoptic area on male sexual behavior

Morphiceptin, a selective mu opioid agonist, injected into the medial preoptic area (MPOA), delayed the onset of copulation in male rats, but did not affect genital reflexes, sexual motivation or general motor activity. In a dose-dependent manner, morphiceptin (100 ng and 1000 ng) injected into the MPOA increased mount and intromission latencies. Similar injections of morphiceptin into the ventromedial hypothalamus had no effect on any parameter of copulation. The increase in copulatory latencies following the injection of the highest dose of morphiceptin was blocked by pretreatment with the opioid antagonist naloxone. In the X-maze task, morphiceptin had no effect on sexual motivation, as measured by the percentage of trials on which the male chose the female's chamber, but it increased the number of trials in which the subject did not select a chamber within 60 s and the latency to the female the first time he chose her chamber. Similar to the copulation task, the mount and intromission latencies were also increased in the X-maze, after the male reached the female. Morphiceptin in the MPOA had no effect on ex copula genital reflexes, tested in restrained supine males, or on motor activity, tested in a grid box. These results suggest that morphiceptin disrupts either the specific copulatory somatomotor pattern or a more general motivational component.     

Diurnal rhythm in cyclic GMP/nitric oxide efflux in the medial preoptic area of male rats

Since nitric oxide (NO) is implicated in the neuroendocrine control of luteinizing hormone-releasing hormone (LHRH) secretion and sexual behavior which show diurnal variations, we monitored cGMP levels (an index of NO activity) in the extracellular compartment of the medial preoptic area (MPOA) using microdialysis. It was observed that MPOA cGMP levels rose significantly in the afternoon in both castrated and intact male rats, thereby suggesting the existence of a diurnal rhythm in MPOA cGMP/NO efflux which may participate in eliciting the well-known diurnal variations in LHRH neuronal activity and male sexual behavior.     

Atherogenic lipids and lipoproteins in hemodialysis patients

Different hypotheses have been put forward trying to explain the mechanisms associated with the disruption of male sexual behavior after lesions of the medial preoptic area (MPOA). It has been suggested that sexual motivation, motor execution or both are affected by MPOA lesions. In the present experiment, the socio-sexual behavior of male rats bearing extensive MPOA lesions, that abolished sexual behavior, was compared with that of sham-lesioned animals and to prelesion levels. The socio-sexual interactions were recorded for 10 min in one prelesion and two postlesion tests. The frequency and duration of the following behaviors were recorded: rearing, sniffing, self-grooming, grooming partner, genital exploration, pursuit and resting. The analysis of the socio-sexual interactions showed that the frequency and duration of pursuit was reduced in the first and second tests after the lesion in comparison to both prelesion levels and to a sham-lesioned group. There is strong evidence that pursuit is the only precopulatory behavior that can consistently predict the appearance of sexual behavior. When pursuit is reduced the transition from the precopulatory to the copulatory phase is made more difficult. Therefore, it appears that the MPOA lesions reduce the subject's motivation to engage in sexual behavior.     

Restoration of sexual behavior and dopaminergic neurotransmission by long term exogenous testosterone replacement in aged male rats

PURPOSE: We investigated the effects of long-term testosterone replacement on copulatory behavior and dopaminergic neurotransmission in the medial preoptic area of aged male rats. MATERIALS AND METHODS: The rats were divided into 3 groups depending on testosterone replacement. Those in the long-term replacement group were castrated at the age of 12 months and received testosterone replacement thereafter for 12 months. In the short-term replacement group, rats were castrated at the age of 22 months and high or low dose testosterone replacement was done for 2 months. The control group consisted of aged rats 24 months old and young rats 12 weeks old, neither of which had been castrated or received testosterone replacement. We observed sexual behavior in rats of these groups. After a behavioral test, we measured the tissue concentration of dopamine in the MPOA and the change rate of the extracellular dopamine level induced by infusion of N-methyl-D-aspartic acid (NMDA) in the MPOA and compared the long-term replacement and no-replacement groups. RESULTS: The rats in the long-term replacement group showed a mount rate at the same level as that of young rats at 6 weeks after starting replacement and it was maintained to 24 months of age. Their mount rate was significantly higher than that of the rats with the short-term replacement. A significantly higher change rate of dopamine release was recognized in the long-term group; however, no significant difference in the concentration of dopamine was recognized between aged rats with long-term replacement and those without replacement. CONCLUSIONS: Aged rats (24 months old) with long-term testosterone replacement maintained almost the same level of mount behavior as young rats (12 weeks old). The results imply that long-term testosterone replacement may favorably alter the decline in the process of sexual activity with aging. The restoration by testosterone replacement of dopaminergic activity in the MPOA may be involved in the maintenance of sexual function in aged rats.     

Medial preoptic area oxytocin and female sexual receptivity.

Intracerebroventricular (icv) administration of the nonapeptide oxytocin (OXT) increases sexual receptivity in female rats. The medial preoptic area (MPOA) appeared to be the most sensitive brain area to the facilitative effects of OXT. Bilateral infusions of 100 ng of OXT into the MPOA significantly elevated lordosis quotients in overiectomized (OVX), estrogen-treated rats. This dose of OXT was ineffective when infused icv or into the ventromedial hypothalamus, mesencephalic central gray, or ventral tegmental area. A 500-ng dose of OXT significantly elevated lordosis responding when infused icv, corresponding with our previous findings. Mounting by males significantly increased immunoreactive levels of OXT and decreased the number of OXT immunostaining cells in the MPOA of sexually receptive rats pretreated with estrogen and progesterone. The MPOA is a primary site of the OXT facilitation of sexual receptivity where OXT may be released during mating. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential sensitivity to the wake-promoting actions of norepinephrine within the medial preoptic area and the substantia innominata.

Mapping studies were conducted to delineate the site(s) of action for the arousal-enhancing actions of norepinephrine (NE) within the basal forebrain region encompassing the medial preoptic area (MPOA) and the substantia innominata (SI). Varying doses of NE, the β-agonist, isoproterenol, or the α?-agonist, phenylephrine, were infused into the MPOA or SI in the resting rat. Infusions of NE (4 nmol, 16 nmol/150 nl), isoproterenol (15 nmol/150 nl), and phenylephrine (40 nmol/250 nl) into the MPOA elicited robust increases in waking. In contrast, neither isoproterenol or phenylephrine infusions into the SI altered behavioral state. NE infusions into the SI increased waking only at the highest dose, and at this dose there was an anatomical gradient for NE-induced waking, with infusions placed farther from the MPOA, producing smaller increases in waking. Thus, in contrast to the MPOA, the SI is relatively insensitive to the wake-promoting actions of NE. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A Nitric Oxide Synthesis Inhibitor in the Medial Preoptic Area Inhibits Copulation and Stimulus Sensitization in Male Rats.

Dopamine in the medial preoptic area (MPOA) facilitates copulation in male rats, and nitric oxide (NO) regulates basal and female-stimulated MPOA dopamine release. Microinjection of L-nitro-arginine methyl ester (L-NAME, an NO synthesis inhibitor) into the MPOA blocked copulation in naive rats and impaired copulation in sexually experienced males. In other naive rats, L-NAME or saline was microinjected into the MPOA before each of 7 daily exposures to a receptive female placed over their cage. In a drug-free test on Day 8, copulation by L-NAME-treated rats was similar to that of unexposed controls and was impaired relative to saline-treated males. Therefore, NO in the MPOA is important for copulation and stimulus sensitization in male rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Microinfusion of cocaine into the medial preoptic area or nucleus accumbens transiently impairs maternal behavior in the rat.

Cocaine was microinfused bilaterally (50 μg/0.5 μl/side) into the medial preoptic area (MPOA) or nucleus accumbens (NA), 2 regions within the rat brain neural circuit known to mediate maternal behavior (MB). Additionally, 2 sites not involved in this neural circuit, the dorsal striatum and dorsal medial hippocampus, were used as control sites. Microinfusion of cocaine into the MPOA or NA impaired MB, whereas infusion into the control sites did not. MB impairment was not temporally coincident with the increased locomotor activity, also documented after cocaine infusion into the MPOA or NA, arguing strongly that impaired MB is a direct, specific effect of cocaine in these areas, not a derivative of increased motor activity. This is the first demonstration that cocaine action on single central nervous system (CNS) sites can impair MB to the same extent as systemic injections. Thus, cocaine's simultaneous effect on multiple CNS sites is not required for MB impairment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)