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)     

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)     

Nitric oxide mediates sexual behavior in female rats

Nitric oxide (NO), an active free radical formed during the conversion of arginine to citrulline by the enzyme NO synthase (NOS), mediates vasorelaxation, cytotoxicity, and neurotransmission. Neurons containing NOS (NOergic) are located in the hypothalamus. These NOergic neurons control the release of several hypothalamic peptides. Release of NO from these NOergic neurons stimulates pulsatile release of luteinizing hormone-releasing hormone (LHRH) in vivo and LHRH release in vitro. LHRH not only induces LH release, which induces ovulation, but also facilitates female sexual behavior. Sexual behavior can be induced reliably in estrogen-primed ovariectomized female rats by progesterone (P). This behavior consists of proceptive behavior to attract the male and the assumption of a clear characteristic posture, lordosis, when mounted by the male. To ascertain the role of NO in the control of sexual behavior in female rats, an inhibitor of NOS, NG-monomethyl-L-arginine was microinjected into the third cerebral ventricle (3V) of conscious, ovariectomized, estrogen-primed rats with indwelling cannulae. NG-Monomethyl-L-arginine (10-1000 micrograms) prevented P-facilitated lordosis when administered intracerebroventricularly into the 3V, 20 min prior to the 3V injection of P. NG-Monomethyl-D-arginine, which does not inhibit NOS, did not inhibit lordosis under the same experimental conditions. Microinjection into the 3V of sodium nitroprusside (SNP), which spontaneously releases NO, facilitated lordosis in estrogen-primed rats in the absence of P. The facilitation of lordosis induced by either P or SNP was prevented by intracerebroventricular injection of hemoglobin, which binds NO. Lordosis facilitated by P or SNP was blocked by injection of LHRH antiserum into the 3V. The results are interpreted to mean that the P-facilitated lordosis response is mediated by LHRH release. Furthermore, since NO release from SNP also facilitates lordosis in the absence of P and this response could be blocked by LHRH antiserum, we conclude that P brings about the release of NO, which stimulates LHRH release that facilitates lordosis. Thus, the results indicate that NO induces LHRH release and that LHRH then plays a crucial role in mediation of sexual behavior in the female rats.     

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)     

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)     

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.     

Opioids and sexual behavior of male rats: Involvement of the medial preoptic area.

Local infusion of β-endorphin (β-END) into the medial preoptic area (MPOA) dose-dependently impaired the gating of the copulatory response and the execution of the sexual performance of sexually experienced, intact male rats. Local naloxone treatment prevented the impairment of the sexual response by β-END, but failed to facilitate unimpaired copulation. Local infusion into the MPOA of equimolar doses of α-endorphin, dynorphin-A-(1-17) or met-enkephalin were less effective than β-END. It is suggested that endogenous opioid systems in the MPOA are normally quiescent, and increased activity may be related to disrupted or inhibited male sexual behavior. (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)     

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.     

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)     

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)     

Effect of medial preoptic lesions on sexual behavior of female rats is determined by test situation.

Examined the sexual behavior of 47 female Long-Evans rats with bilateral lesions in the medial preoptic area (MPOA) and 27 Long-Evans sham-operated Ss (controls) in 2 testing conditions. In the 1st condition, in which the S could not leave the vicinity of males (no-exit test), lordosis quotients (LQs) were elevated in relation to baseline levels for MPOA Ss. In the 2nd condition, in which the female could control her proximity to males (exit test), MPOA LQs were not different from control levels, and experimental Ss permitted fewer copulatory contacts, exhibited less frequent solicitational behavior, and spent less time with males than the controls did. These findings suggest that the higher LQs seen in no-exit tests as a result of MPOA damage are not due to a lesion-induced potentiation in the Ss' preference to engage in sexual contacts with males. (27 ref) (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)     

Nocturnal decreases in nitric oxide and cyclic GMP contents in the chick brain and their prevention by light

The diurnal variations in the contents of nitric oxide (NO) and cyclic GMP were studied in the chick brain. NO and cyclic GMP contents in the chick brain were lower at night than during the day and were inversely correlated with high night-time tissue melatonin levels. Furthermore, when animals were kept in light at night, tissue melatonin levels remained at low diurnal values, whereas NO and cyclic GMP contents remained high. Since we have previously shown that physiological concentrations of melatonin inhibit nitric oxide synthase (NOS) activity in different brain areas, the nocturnal decrease in brain NO and cyclic GMP contents may be, in part, a consequence of the nocturnal inhibitory effect of melatonin on NOS activity.     

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.     

Behavioral effects of alpha-MSH and MCH after central administration in the female rat

The behavioral effects of alpha-MSH, MCH, and alpha-MSH + MCH were investigated in the ventromedial nucleus (VMN) and medial preoptic area (MPOA) (bilateral, 100 ng in 0.5 microliter). Infusion of alpha-MSH into the VMN increased aggressive behavior; in the MPOA it reduced exploration and increased anxiety. In both areas it stimulated sexual behavior. MCH also stimulated sexual behavior in the MPOA and VMN and had an anxiogenic effect in the MPOA. The effect of alpha-MSH on aggression and exploration was antagonized by MCH. When given together, the two peptides were mutually antagonistic on anxiety. This study indicates that MCH has central nervous system effects and may be a partial alpha-MSH agonist.     

Inhibition of nitric oxide synthase within the medial preoptic area impairs pup retrieval in lactating rats.

Central suppression of nitric oxide (NO) production by administering 250 μg of Nitrow-L-Argenine Methyl Ether (L-NAME), an inhibitor of NO synthase, into the 3rd ventricle disrupts both pup retrieval and maternal aggression in postpartum rats. In these studies, the authors examined the ability of varying doses of L-NAME to produce these effects on maternal behavior. Doses of L-NAME that were shown to be ineffective when injected into the 3rd ventricle were administered bilaterally into the medial preoptic area (MPOA) of rats on Day 4 postpartum. To assess the specificity of L-NAME's effect within the MPOA, the authors bilaterally injected Nitrow-D-Argenine Methyl Ether (D-NAME), an inactive isomer of L-NAME, into the MPOA. When administered intracerebroventricularly, the 2 highest doses of L-NAME used, 250 μg and 200 μg, disrupted retrieval behavior and maternal aggression. Bilateral injections of L-NAME into the MPOA at doses of 20 μg and 40 μg/side also disrupted pup retrieval, and D-NAME injections into the MPOA had no effect on the maternal behaviors measured. All rats in these experiments showed normal maternal behavior 24 hr after drug administration. These results suggest that NO acts within the MPOA to facilitate retrieval behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

Regulation of the endogenous NO pathway by prolonged inhaled NO in rats

Nitric oxide (NO) modulates the endogenous NO-cGMP pathway. We determined whether prolonged inhaled NO downregulates the NO-cGMP pathway, which may explain clinically observed rebound pulmonary hypertension. Rats were placed in a normoxic (N; 21% O2) or hypoxic (H; 10% O2) environment with and without inhaled NO (20 parts/million) for 1 or 3 wk. Subsequently, nitric oxide synthase (NOS) and soluble guanylate cyclase (GC) activity and endothelial NOS (eNOS) protein levels were measured. Perfusate cGMP levels and endothelium-dependent and -independent vasodilation were determined in isolated lungs. eNOS protein levels and NOS activity were not altered by inhaled NO in N or H rats. GC activity was decreased by 60 +/- 10 and 55 +/- 11% in N and H rats, respectively, after 1 wk of inhaled NO but was not affected after 3 wk. Inhaled NO had no effect on perfusate cGMP in N lungs. Inhaled NO attenuated the increase in cGMP levels caused by 3 wk of H by 57 +/- 11%, but there was no rebound in cGMP after 24 h of recovery. Endothelium-dependent vasodilation was not altered, and endothelium-independent vasodilation was not altered (N) or slightly increased (H, 10 +/- 3%) by prolonged inhaled NO. In conclusion, inhaled NO did not alter the endogenous NO-cGMP pathway as determined by eNOS protein levels, NOS activity, or endothelium-dependent vasodilation under N and H conditions. GC activity was decreased after 1 wk; however, GC activity was not altered by 3 wk of inhaled NO and endothelium-independent vasodilation was not decreased.