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)     

Cholinergic influences on estrogen-dependent sexual behavior in female rats.

Examined the ability of cholinergic agents to influence hormone-dependent sexual behavior in Sherman rats. In Exp I, sexual behavior, indicated by the incidence of lordosis, was significantly increased in estrogen-treated Ss following bilateral infusion of a cholinergic receptor agonist, carbachol (.5 μg/cannula) into the medial preoptic area of the brain. Infusion of an artificial cerebrospinal fluid vehicle failed to facilitate lordosis. The incidence of lordosis was normally highest 15 min after carbachol infusion began to wane by 45 min, and had returned to control levels by 90 min. Centrally administered carbachol activated lordosis at lower levels of estrogen priming than did systemically administered progesterone. In Exp II, Ss brought into sexual receptivity by administration of estrogen and progesterone received preoptic infusions of an acetylcholine synthesis inhibitor, hemicholinium-3 (HC-3). Significant reductions in the incidence of lordosis were observed following bilateral infusion of HC-3 (1.25 μg/cannula). This inhibition of lordosis was prevented when carbachol (.5 μg/cannula) was infused along with HC-3. Results confirm the importance of cholinergic influences on sexual behavior in female rats. (20 ref) (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)     

Localization in the amygdala of the amnestic action of diazepam on emotional memory

Electrical lesions of the medial preoptic area/anterior hypothalamus (MPOA/AH) have been reported to enhance the display of steroid-induced lordosis in castrated male rats. This study employed the cell body-specific neurotoxin, ibotenic acid, to ascertain whether neurons originating in this region (as opposed to axons of passage) tonically inhibit steroid-induced lordosis in adult male rats. Castrated, adult Long-Evans males received bilateral electrical lesions or injections of ibotenic acid or vehicle aimed at the MPOA/AH. Following administration of estradiol benzoate (EB) and progesterone, lordosis quotients (LQs) and lordosis ratings (LRs) were significantly higher in groups of rats with electrical lesions (LQ = 62.2 +/- 15.1; LR = 1.22 +/- 0.34) and ibotenic acid-induced lesions (LQ = 58.1 +/- 12.2; LR = 0.99 +/- 0.24) than in the control group (LQ = 12.8 +/- 7.3; LR = 0.22 +/- 0.13). To determine whether this enhancement of receptive behavior in MPOA/AH-lesioned males was an effect on estradiol-induced, as compared to progesterone-facilitated lordosis, groups of castrated rats in a second experiment received bilateral injections of ibotenic acid or vehicle aimed at the MPOA/AH and were tested for lordosis after administration of EB alone and again after injection of progesterone. Following treatment with EB alone, rats with ibotenic acid-induced MPOA/AH lesions tended to be slightly less receptive than control animals. However, following injections of progesterone, LQs and LRs were higher in the MPOA/AH-lesioned group than in the control animals, as had been observed in the first experiment.(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

Hypophysectomy facilitates sexual behavior in female rats

Lordosis was elecited in 49% of 87 hormonally untreated, hypophysectomized-ovariectomized (hypox-ovx) female rats in response to palpation of the flanks and perineum (vaginal stimulation was not applied). By contrast, only 12% of 113 hormonally untreated ovariectomized (ovx) rats showed lordosis in response to such stimulation. Subsequently, hypox-ovx and ovx-only rats were given daily injections of 1 mug/kg estradiol benzoate (EB) and tested for sexual receptivity with males. Teh estrogen-treated hypox-ovx females became sexually receptive significantly earlier, and exhibited higher lordosis quotients and more soliciting behavior, than the estrogen-treated ovx-only rats. The increased sexual responsiveness in the hypox-ovx rats could be due to increased LRH activity. To test this, we treated hypox-ovx rats with dihydrotestosterone propionate (DHT-P), which suppresses plasma LH levels but is relatively ineffective in inducing sexual receptivity, and found a significant depression of lordosis responsiveness. These experiments suggest that hypox-ovx females show a heightened responsiveness to hormonal and/or sensory factors that induce a lordosis response, possibly because of increased LRH activity.     

Differential effects of beta-endorphin and Met- and Leu-enkephalin on steroid hormone-induced lordosis in ovariectomized female rats

The effect of intrathirdventricular (I.T.V.) injections of beta-endorphin, anti-beta-endorphin antiserum, Met-enkephalin, Leu-enkephalin, and naloxone on the initial activation and final development of steroid hormone-mediated induction of female sexual receptivity was studied in ovariectomized female rats. The lordosis response to male mounts in ovariectomized rats after subcutaneous (S.C.) estradiol benzoate (EB) and progesterone (Prog) priming was facilitated by beta-endorphin, and Met-enkephalin (10 microg x 5 microl(-1)), but inhibited by Leu-enkephalin, when the peptides were injected into the third ventricle at the time of S.C. EB priming. A lower dose Met-enkephalin had no effects. Lordosis behavior in steroid hormone-primed rats was significantly facilitated when I.T.V. injections of Met-enkephalin were given 1 h prior to behavioral testing (47 h after EB priming). At 1 h prior to behavioral testing (47 h after EB priming), I.T.V. injection of beta-endorphin significantly inhibited lordosis behavior, especially at the higher dose of beta-endorphin (10 microg x 5 microl(-1)). Under those conditions, Leu-enkephalin had no effect. Lordosis behavior of ovariectomized female rats receiving S.C. steroid hormones and I.T.V. injection of anti-beta-endorphin antiserum was significantly inhibited when anti-beta-endorphin antiserum was injected at the time of EB priming. However, lordosis was significantly facilitated when anti-beta-endorphin antiserum was injected 1 h prior to the behavior testing (47 h after EB priming). In contrast, I.T.V. injection of the opioid antagonist naloxone given either at the time of EB priming or 1 h prior to behavioral testing (47 h after EB priming) decreased lordosis behavior. The present results suggest that 1) beta-endorphin, Met-enkephalin, and Leu-enkephalin have differential effects in the control of lordosis behavior; 2) the opioidergic systems may modulate initial-stage and final-stage estrogen-induced lordosis behavior; and 3) the opioidergic systems could be divided into the endorphinergic modulation-type and enkephalinergic modulation-type, based on their effects on lordosis behavior.     

Effects of a muscarinic antagonist on various components of female sexual behavior in the rat.

Effects of the muscarinic antagonist scopolamine on lordosis, solicitation, pacing, approach, attractivity, and activity were evaluated in ovariectomized rats brought into sexual receptivity with estrogen and progesterone. Systemic (1 mg/rat) or intraventricular (10 μg bilaterally) administration of scopolamine significantly reduced the incidence of lordosis and solicitation behaviors and disrupted typical pacing of sexual contacts with a stimulus male. In addition, females avoided contact with a stimulus male, but not a stimulus female, following intraventricular infusion of scopolamine. The levels of general activity and frequencies of sexual contacts were similar in females treated intraventricularly with scopolamine and vehicle solutions. Consequently, scopolamine disrupted various components of sexual behavior, including lordosis, solicitation, pacing, and approach, without altering female attractivity or general activity. (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)     

Binding of [3H]estradiol by brain cell nuclei and female rat sexual behavior: inhibition by experimental diabetes

In streptozotocin-diabetic female rats acute (24 h) withdrawal of insulin significantly impairs both estradiol + progesterone-induced sexual receptivity and cell nuclear concentration of [3H]estradiol in hypothalamus, preoptic area, and pituitary gland. Omission of insulin treatment for the first 24 h of a 30-h or 54-h estradiol benzoate-conditioning period significantly reduced mean lordosis ratings of ovariectomized-diabetic rats. Insulin withdrawal at the time of progesterone treatment and behavioral testing did not diminish sexual receptivity. One-half or 2 h after an intravenous injection of [3H]estradiol-17beta diabetic rats without insulin exhibited reduced cell nuclear [3H]estradiol concentrations (2 h) and/or diminished cell nuclear/whole homogenate concentration ratios (0.5 and 2 h). Twenty-four hour insulin withdrawal affected neither whole tissue [3H]estradiol uptake nor hypothalamus-preoptic area cytoplasmic estrogen-receptor content. These results: (1) suggest that diminished estradiol binding by target tissue cell nuclei may contribute to the well-known reproductive failures of female diabetics, and (2) support the concept that estradiol acts at the level of brain cell nuclei to induce female sexual behavior.     

Evidence for involvement of midbrain central gray in cholinergic mediation of female sexual receptivity in rats.

Conducted 3 experiments with 63 female Sherman rats to determine the role of the midbrain central gray (MCG) in facilitation of lordosis by cholinergic agonists. Selected findings show that Ss with MCG damage displayed significantly less facilitation than sham-lesion Ss. Pretreatment with scopolamine (SCOP) abolished lordosis facilitation in both groups, and after treatment with estradiol and progesterone, sham-lesion Ss showed more receptivity than MCG-lesion Ss. Systemic injection of SCOP produced a significant decline in lordosis for both groups. Results suggest that the MCG plays an important role in the cholinergic mediation of female sexual receptivity. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Connections between the pontine central gray and the ventromedial hypothalamus are essential for lordosis in female rats.

Lesions and knife cuts were used to study central gray (CG) and ventromedial hypothalamic (VMH) mediation of sexual receptivity in female rats. Lesions of the midbrain–pontine CG eliminated lordosis in female rats. Bilateral sagittal knife cuts that bracketed the rostral pontine CG also eliminated lordosis, and an experiment with the retrograde tracer Fluoro-Gold confirmed the effectiveness of these cuts in severing the lateral connections linking the VMH and the CG. Finally, females with a unilateral hypothalamic cut combined with a contralateral CG transection almost never showed lordosis. Each cut, at a different level for each side of the brain, transected axons linking the VMH and the CG. The demonstration that this combination eliminated lordosis provides new evidence that the lateral connections between the VMH and the CG are essential for the display of sexual receptivity in female rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

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.     

Concurrent inhibition of sexual behavior, but not brain [–3H]estradiol uptake, by progesterone in female rats.

In 7 experiments with ovariectomized female Sprague-Dawley rats, chronic injections of high doses of progesterone (5 mg) and low doses of estradiol benzoate (EB; 2 μg) resulted in less sexual behavior than did low doses of progesterone (.5 mg) and low doses of EB. In a typical procedure for inducing sexual behavior, EB and progesterone were given sequentially, separated by 42 hrs. High levels of progesterone (2.5 and 5 mg) administered concurrently with EB inhibited the induction of sexual receptivity. Increasing the dose of EB from 2 μg to 6 μg or 10 μg offset this inhibition. High doses inhibited the induction of sexual behavior, but the inhibition waned when progesterone was administered 48 hrs prior to EB. A single injection of progesterone (1 mg) that did not inhibit the induction of sexual behavior when administered concurrently with EB did inhibit lordosis when distributed into 5 injections (.2 mg) every 4 hrs. Results of 2 experiments in which progesterone did not inhibit the uptake or retention of [–3H]estradiol by brain cell nuclei suggest that the antiestrogenic action of progesterone in the CNS is not to interfere with the binding of estradiol. (37 ref) (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)     

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)     

Failure of protein synthesis inhibition to block progesterone desensitization of lordosis in female rats

Progesterone's desensitization effect on lordosis has been shown to correlate with a decreased concentration of hypothalamic progestin receptors after progesterone injection. In a recent study, one group of investigators found that the protein synthesis inhibitor anisomycin appeared to block progesterone's desensitization effect. Despite decreased levels of cytoplasmic progestin receptors, progesterone + anisomycin-treated rats exhibited a high level of lordosis four hr after a second progesterone injection. Because this finding conflicts with a progestin receptor model of progesterone's desensitization effect, we investigated it further. In the first experiments, ovariectomized rats were injected with estradiol benzoate followed 24 hr later by either progesterone or vehicle. Anisomycin injected 3 hr after progesterone, at a dose that causes inhibition of hypothalamic protein synthesis for at least 4 hr, was without effect on progesterone desensitization a day later. In other experiments silastic implants containing estradiol were inserted into ovariectomized rats. Forty-five hr later, rats received progesterone or vehicle, followed by injections of anisomycin or saline. Rats receiving anisomycin + progesterone were still highly receptive at 30 hr while saline + progesterone controls were not. Furthermore, the results were similar 4 hr after a second injection of progesterone at 30 hr. In a related experiment, we confirmed that anisomycin delayed dramatically termination of the period of sexual receptivity. In this laboratory anisomycin does not seem to block progesterone's desensitization effect. However, with certain procedures anisomycin delays the termination of sexual receptivity. Thus it is important in investigations of the mechanism of progesterone's desensitization effect that animals be tested prior to the second progesterone injection to determine if they are actually responding to the progesterone.     

Lordosis-enhancing medial preoptic area lesions do not alter hypothalamic estrogen receptor- or progestin receptor-immunoreactivity in prepubertal female guinea pigs

Female guinea pigs rarely display adult-typical lordosis responses to ovarian steroid hormones until 40-50 days of age. Behavioral hyporesponsiveness in prepubertal females may be due, in part, to deficiencies in hypothalamic estrogen receptors and/or estradiol-induced progestin receptors. This study was designed to test the hypothesis that bilateral medial preoptic area (MPOA) lesions, which enhance the display of progesterone-facilitated lordosis in juvenile females, increase levels of hypothalamic estrogen receptors and/or estradiol-induced progestin receptors. Hartley guinea pigs were ovariectomized at 11-12 days of age and at 14-15 days of age received bilateral electrolytic or sham lesions aimed at the MPOA. At approximately 3 weeks of age, lesioned and sham-lesioned animals were either tested for the display of progesterone-facilitated lordosis or perfused, and their hypothalamic tissue processed for estrogen receptor- or estradiol-induced progestin receptor-immunostaining. Although a significantly higher percentage of MPOA-lesioned than sham-lesioned guinea pigs displayed progesterone-facilitated lordosis (85.7% vs. 5. 8%, respectively, p<0.05), there were no significant lesion-related differences in the number or staining intensity of cells containing estrogen receptor- or estradiol-induced progestin receptor-immunoreactivity in the ventrolateral hypothalamus or arcuate nucleus. These data do not support the hypothesis that the enhanced display of progesterone-facilitated lordosis in prepubertal guinea pigs following MPOA lesions is due to increased hypothalamic concentrations of estrogen receptors or estradiol-induced progestin receptors.