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)     

Is sexual motivational state linked to dopamine release in the medial preoptic area?

The medial preoptic area (mPOA) is a key site for the dopaminergic enhancement of male sexual behavior. Dopamine release increases in the rat mPOA with mating, supporting the critical stimulatory role played by preoptic dopamine on male sexual behavior. However, it has been questioned whether dopamine is specifically related to the occurrence of male sexual behavior and not simply involved in general arousal. To address this question, we asked whether dopamine release in the mPOA is linked to the production of male sexual behavior in Japanese quail (Coturnix japonica), a species that exhibits a much shorter temporal pattern of copulation than rats and does not have an intromittent organ, resulting in a very different topography of their sexual response. Extracellular samples from the mPOA of adult sexually experienced male quail were collected every 6 min before, during, and after exposure to a female using in vivo microdialysis and analyzed using high-performance liquid chromatography with electrochemical detection. Extracellular dopamine significantly increased in the presence of a female and returned to baseline after removal of the female. However, quail that failed to copulate did not display this increased release. These findings indicate that it is not solely the presence of a female that drives dopamine release in males, but how a male responds to her. Furthermore, in quail that copulated, dopamine release did not change in samples collected during periods of no copulation. Together, these findings support the hypothesis that dopamine action in the mPOA is specifically linked to sexual motivation and not only to copulatory behavior or physical arousal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex versus sweet: Opposite effects of opioid drugs on the reward of sucrose and sexual pheromones.

Endogenous opioids mediate some reward processes involving both natural (food, sweet taste) and artificial (morphine, heroin) rewards. In contrast, sexual behavior (which is also reinforcing) is generally inhibited by opioids. To establish the role of endogenous opioids for a newly described natural reinforcer, namely male sexual pheromones for female mice, we checked the effects of systemic injections of the general opioid antagonist naloxone (1-10 mg/kg) and the agonist fentanyl (0.1- 0.5 mg/kg) in a number of behavioral tests. Naloxone affected neither the innate preference for male-soiled bedding (vs. female-soiled bedding) in 2-choice tests nor the induction of place conditioning using male pheromones as rewarding stimuli, although it effectively blocked the preference for consuming a sucrose solution. In contrast, fentanyl inhibited the preference for male chemosignals without altering sucrose preference. These results suggest that, in macrosmatic animals such as rodents, opioidergic inhibition of sexual behavior might be due, at least partially, to an impaired processing of pheromonal cues and that the hedonic value of sweet-tasting solutions and sexual pheromones are under different opioid modulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

μ Opioid receptors in the ventrolateral periaqueductal gray mediate stress-induced analgesia but not immobility in rat pups.

Rat pups become immobile and analgesic when exposed to an adult male rat. The aim of this study was to determine whether these reactions are under the control of endogenous opioids and to determine the role of the midbrain periaqueductal gray (PAG), which mediates stress-induced immobility and analgesia in adult animals. In Experiment 1, 14-day-old rats were injected systemically with the general opioid receptor antagonist naltrexone (1 mg/kg), which blocked male-induced analgesia to thermal stimulation but did not affect immobility. In Experiment 2, the selective μ opioid receptor antagonist {d}-Phe-Cys-Tyr-{d}-Trp-Orn-Thr-Pen-Thr-NH? (CTOP; 50 or 100 ng/200 nl) was microinjected into the ventrolateral and lateral PAG. CTOP suppressed male-induced analgesia when injected into the ventrolateral PAG. Male-induced immobility was not affected by CTOP. Male proximity therefore seems to induce analgesia in rat pups by releasing endogenous opioids that bind to μ opioid receptors in the ventrolateral PAG. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of ibotenic acid lesions of the nucleus accumbens on paced mating behavior in the female rat.

The present study investigated the role of the nucleus accumbens (NAcc) in paced mating behavior in female rats. A sexually receptive female rat will approach and withdraw from a sexually active male, thereby controlling the timing of the receipt of sexual stimulation (e.g., mounts, intromissions, ejaculations). In this study, ibotenic acid lesions in the NAcc core increased the likelihood that a female rat would withdraw from a male rat after a mount but did not affect contact return latency or sexual receptivity. lbotenic acid lesions in the NAcc shell did not affect paced mating behavior or sexual receptivity. The results suggest that the NAcc core plays a role in suppressing withdrawal behavior in response to less intense mating stimulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Naloxone blocks place preference conditioning after paced mating in female rats.

Sexual behavior in male rats induces a positive affect as evaluated by conditioned place preference (CPP). In addition, when females control or "pace" the rate of sexual interaction, a clear CPP is also observed. The reward state induced by mating in male rats is blocked by the injection of the opioid antagonist naloxone. In the present experiment, a dose of 4 mg/kg of naloxone completely blocked the CPP induced in females by paced mating. It appears that a common opioid system is involved in the positive affect induced by sexual behavior in both male and female rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Multicentric Castleman''s disease with lymphoid interstitial pneumonia and polyneuropathy

During emergencies in their natural environments, vertebrates initiate coping mechanisms that redirect behavior away from nonessential activities and towards survival. Reproductive behaviors are suppressed. Evidence from field studies on passerine birds shows that this inhibition may not depend on the suppression of gonadal sex steroids, since during the breeding season they remain elevated despite activation of the stress response. We hypothesize that an alternate, central mechanism mediates the inhibition of reproductive behavior during stress in passerines. In this study, we tested the intracerebroventricular effects of endogenous opioids and corticotropin-releasing factor (CRF), neuropeptides implicated in the stress response, on courtship behavior in wild-caught female white-crowned sparrows. Beta-endorphin (beta-EN) significantly inhibited copulation solicitation, an estrogen-dependent courtship display, 30 min after treatment. Naloxone, an opioid antagonist, enhanced the behavior. CRF caused a suppression of solicitation that was reversible by pretreatment with naloxone, suggesting an intermediary role for endogenous opioids in CRF-induced suppression of courtship. The effects of beta-EN and CRF on solicitation appear to be independent of any general effects on locomotor activity. These results support our hypothesis that stress neuropeptides orchestrate coping behaviors in wild birds.     

Actions of endogenous opioids on NMDA receptor-independent long-term potentiation in area CA3 of the hippocampus

The opioid peptides represent a major class of neurotransmitter in the vertebrate nervous system and are prevalent in the hippocampus. There is considerable interest in the physiological function of the opioids contained in the mossy fiber pathway. The release of opioids from mossy fibers shows a strong frequency dependence. Long-term potentiation (LTP) at this synapse, an NMDA receptor-independent form of LTP, also depends on high-frequency synaptic activity, and this has led to speculation that endogenous opioids may be a critical factor in LTP induction. Previous reports using extracellular recordings have provided evidence for and against a role for opioids in mossy fiber LTP. Using single-cell recording techniques, we have tested the hypothesis that endogenous opioids are required for mossy fiber LTP induction. We recorded from a defined population of synapses that had EPSCs with fast rise times, short latencies, and monophasic decays, consistent with a proximally terminating synapse. The opioid antagonist naloxone prevented mossy fiber LTP in the rat, but had no effect on the commissural/associational system, a nonopioid-containing pathway. The action of naloxone was not mediated through disinhibition because GABAA receptors were pharmacologically blocked in these experiments. We also tested the hypothesis that variations in postsynaptic receptor subtype distribution between species might explain previous controversies regarding the role of endogenous opioids. In contrast to the rat, LTP of the mossy fiber field potential in guinea pig was not blocked by naloxone. Our data suggest that opioids may be the presynaptically released, frequency-dependent, associative factor for mossy fiber LTP induction.     

Endogenous opioid peptides acting at mu-opioid receptors in the dorsal horn contribute to midbrain modulation of spinal nociceptive neurons

Activation of neurons in the midbrain periaqueductal gray (PAG) inhibits spinal dorsal horn neurons and produces behavioral antinociception in animals and analgesia in humans. Although dorsal horn regions modulated by PAG activation contain all three opioid receptor classes (mu, delta, and kappa), as well as enkephalinergic interneurons and terminal fields, descending opioid-mediated inhibition of dorsal horn neurons has not been demonstrated. We examined the contribution of dorsal horn mu-opioid receptors to the PAG-elicited descending modulation of nociceptive transmission. Single-unit extracellular recordings were made from rat sacral dorsal horn neurons activated by noxious heating of the tail. Microinjections of bicuculline (BIC) in the ventrolateral PAG led to a 60-80% decrease in the neuronal responses to heat. At the same time, the responses of the same neurons to iontophoretically applied NMDA or kainic acid were not consistently inhibited. The inhibition of heat-evoked responses by PAG BIC was reversed by iontophoretic application of the selective mu-opioid receptor antagonists, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) and D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP). A similar effect was produced by naloxone; however, naloxone had an excitatory influence on dorsal horn neurons in the absence of PAG-evoked descending inhibition. This is the first demonstration that endogenous opioids acting via spinal mu-opioid receptors contribute to brain stem control of nociceptive spinal dorsal horn neurons. The inhibition appears to result in part from presynaptic inhibition of afferents to dorsal horn neurons.     

Electron microscopic distribution of mu opioid receptors on noradrenergic neurons of the locus coeruleus

The distribution of mu opioid receptors was examined by light and electron microscopic autoradiography in the locus coeruleus of the rat following in vitro labelling with the iodinated agonist [125I]FK-33824. At the light microscopic level, specific mu opioid binding sites were concentrated over the perikarya and dendrites of neurons that were tyrosine hydroxylase-immunopositive in adjacent sections. Accordingly, both the number of tyrosine hydroxylase-immunoreactive neurons and the density of labelled mu receptors decreased markedly throughout the rostrocaudal extent of the nucleus following treatment with the catecholaminergic neurotoxin 6-hydroxydopamine. By electron microscopy, specifically labelled receptors were detected both inside and on the surface of locus coeruleus neurons. Intracellular sites were found by resolution circle analysis to be highly concentrated within the endoplasmic reticulum and Golgi apparatus, suggesting that the ligand recognizes both glycosylated and preglycosylated forms of receptor. The remainder were found mainly over the cytoplasmic matrix or intracytoplasmic vesicles, and were attributed to newly synthesized or recycled receptors in transit. Cell surface receptors were present over both dendritic and perikaryal membranes of noradrenergic cells. These were most highly concentrated opposite abutting axon terminals, suggesting the existence of receptor 'hot spots' at sites of putative endogenous ligand release. However, only a small proportion of these sites was associated with synaptic specializations. Furthermore, an important contingent was detected opposite non-axonal elements, such as dendrites and glial cells, suggesting that mu opioid ligands act mainly parasynaptically on locus coeruleus neurons. Finally, approximately 5% of labelled receptors were associated with axoglial interfaces, indicating that a minor action of mu opioids in the locus may be presynaptic and/or glial.     

Conditioned place preference for mating is preserved in rats with pelvic nerve transection.

Female rats exhibit a conditioned place preference (CPP) for a context paired with mating. The present experiment tested the hypothesis that the activation of the pelvic nerve mediates the reinforcing effects of mating for female rats. Rats underwent bilateral pelvic nerve or sham transection and then received paced mating, nonpaced mating, or the control treatment during a CPP procedure. Pelvic nerve transection did not affect the CPP for paced or nonpaced mating. In tests of paced mating behavior, contact-return latencies following intromissions were significantly shorter in rats with pelvic nerve transection than they were in rats with sham transections. These results show that the pathway conveying the reinforcing effects of mating stimulation does not depend on the integrity of the pelvic nerve, but that activation of the pelvic nerve contributes to the display of paced mating behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Expression of the human antigen SPAG2 in the testis and localization to the outer dense fibers in spermatozoa

There is increasing evidence to suggest that opioid peptides may have widespread effects as regulators of growth. To evaluate the hypothesis that endogenous opioids control cellular proliferation during neural development, we have used in situ hybridization to examine opioid peptide and receptor mRNA expression in neuroepithelial zones of fetal rat brain and spinal cord. Our data show that proenkephalin mRNA is widely expressed in forebrain germinal zones and choroid plexus during the second half of gestation. In contrast, prodynorphin mRNA expression is restricted to the periventricular region of the ventral spinal cord. Little mu or delta receptor mRNA expression was detected in any regions of neuronal proliferation prior to birth. However, kappa receptor mRNA is widely expressed in hindbrain germinal zones during the 3rd week of gestation. Our present findings support the hypothesis that endogenous opioids may regulate proliferation of both neuronal and non-neuronal cells during central nervous system development. Given the segregated expression of proenkephalin mRNA in forebrain neuroepithelium and kappa receptor mRNA within hindbrain, different opioid mechanisms may regulate cell division in rostral and caudal brain regions.     

An NMDA antagonist impairs copulation and the experience-induced enhancement of male sexual behavior in the rat.

Sexual experience facilitates subsequent male sexual behavior; activation of the N-methyl-D-aspartate (NMDA) glutamate receptor may play a role in this experience-induced enhancement. In this article, the authors report that systemic injections of MK-801, an NMDA receptor antagonist, impaired male sexual behavior in sexually naive and sexually experienced male rats. Furthermore, saline-treated rats that received 7 daily exposures to an inaccessible estrous female instead of sexual experience displayed enhancement of copulation on the following day. Injections of MK-801 before each of these exposures inhibited the experience-induced enhancement on the drug-free test on Day 8. These data suggest that stimulation of NMDA receptors enhances sexual performance immediately and mediates the experience-induced enhancement of subsequent copulatory behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Habituation to chemosensory stimuli in the rat fetus: Effects of endogenous kappa opioid activity.

On Day 21 of gestation, rat fetuses respond to chemosensory stimuli by expressing stereotypic facial wiping behavior. A series of 4 experiments was conducted to investigate (1) the influence of morphine on fetal responsiveness to a single chemosensory infusion, (2) the effect of naloxone blockade of endogenous opioid activity on diminished fetal responsiveness over a series of chemosensory infusions, (3) the effect of endogenous opioids on the recovery of fetal responsiveness to infusion after various dishabituation procedures, and (4) the influence of selective mu and kappa opioid receptor antagonists on fetal habituation. These experiments confirm that fetuses habituate after a brief series of chemosensory infusions and that dishabituation promoted by presentation of a novel stimulus is facilitated by pharmacological blockade of kappa opioid receptors. Endogenous activity in the kappa opioid system may be functional in modulating the sensory environment around the time of birth. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of sequential preoptic and mammillary lesions on male rat sexual behavior.

Observed the sexual behavior of 52 male Sprague-Dawley rats prior to and following bilateral medial preoptic, unilateral medial preoptic, bilateral posterior preoptic, bilateral mammillary, and sham lesions. Bilateral medial preoptic lesions and mammillary lesions were made either simultaneously or sequentially within the same Ss in separate groups. Mammillary lesions had no effect on sexual behavior. Complete destruction of the medial preoptic area made prior to, simultaneous with, and following mammillary lesions completely abolished mating behavior. Partial destruction of the medial preoptic area increased mount and intromission latencies and slightly increased ejaculation latency. Results suggest that since there was no change in the postejaculatory-refractory interval, the medial preoptic area mediates sexual arousal but apparently is not involved in a copulatory-ejaculatory mechanism. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interactions between central opioidergic and cholecystokininergic systems in rats: possible significance for the development of of opioid tolerance

Numerous data suggest that cholecystokinin (CCK) acts as an opioid-modulating peptide. Because pharmacological and behavioural studies have shown that CCK reduces the analgesic effects of opioids, an opioid-mediated activation of CCK-containing neurones has been proposed to be responsible for the development of opioid tolerance. In an attempt to directly assess this hypothesis, we have examined, in naive or morphine-tolerant/dependent rats, the possible influence of opioid-receptor ligands on--1 the release of CCK from spinal cord slices and--2 the extracellular levels of CCK in the frontal cortex in awake, freely moving animals. Whereas the stimulation of mu or delta 1 receptors inhibited the release of the peptide, the stimulation of delta 2 receptors increased CCK release. Morphine also increased CCK release, via an action at delta 2 receptors. The blockade of delta 1 receptors resulted in an enhancement of the peptide release, suggesting that endogenous opioids probably exert inhibitory tonic influence on CCK release through the stimulation of delta 1 receptors. In rats rendered tolerant/dependent, the inhibitory effects of opioids on CCK release, due to the stimulation of mu or delta 1 receptors, and the enhancing effect of delta 1 receptor blockade, were no longer present. In contrast, the delta 2-mediated increase in CCK release persisted. Thus, in morphine-tolerant/dependent rats, opioids apparently retain only their excitatory effects on CCK-containing neurones. These data support the idea that morphine exerts an excitatory influence on central CCKergic neurones, which could tend to reduce the analgesic action of the alkaloid, and are in line with the hypothesis that morphine tolerance/dependence is associated with an activation of CCK-containing neurones.     

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 compulsivity, state affect, and sexual risk behavior in a daily diary study of gay and bisexual men.

Researchers have identified a strong link between sexual compulsivity (SC) and risky sexual behavior among men who have sex with men (MSM). Meanwhile, affect/mood has also been connected with negative sexual health outcomes (sexually transmitted infection/human immunodeficiency virus [HIV] transmission, sexual risk, sex under the influence of drugs/alcohol). Given that SC is characterized by marked distress around one's own sexual behavior, affect may play a central role in SC and HIV risk behavior. Data were taken from the Pillow Talk Project, a pilot study conducted in 2008–2009 with 50 highly sexually active MSM (9 or more male sex partners, ≤ 90 days), of which half displayed SC symptoms and half did not. Forty-seven men completed a daily diary online for 30 days (n = 1,060 diary days), reporting on their sexual behavior and concurrent affect: positive activation, negative activation, anxious arousal, and sexual activation. We conducted HLM analyses using daily affect (Level 1, within subjects) and SC and HIV status (Level 2, between subjects) to predict sexual behavior outcomes. Increased negative activation (characterized by fear, sadness, anger, and disgust) was associated with reduced sexual risk behavior, but less so among sexually compulsive MSM. Sexual activation was associated with increased sexual risk taking, but less so among sexually compulsive MSM. Anxious arousal was associated with increased sexual behavior, but not necessarily sexual risk taking. Findings indicate that affect plays key roles in sexual behavior and sexual risk taking; however, the association between affect and behavior may be different for sexually compulsive and non-sexually compulsive MSM. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Regulation of opioid receptors in rat sensory neurons in culture

To determine whether opioid receptors in sensory neurons are regulated by chronic exposure to opioids, we assessed the binding of various opioid ligands to membranes derived from isolated rat dorsal root ganglia neurons grown in culture. Equilibrium binding of [3H]diprenorphine onto membranes from cells grown for 13-15 days revealed a saturable binding site with a Kd value of 0.3 +/- 0.2 nM and an approximate Bmax value of 1300 +/- 200 fmol/mg of protein. [3H]Diprenorphine binding increased 3-fold from 1-15 days in culture. The mu receptors represent approximately 70 +/- 11% of the [3H]diprenorphine binding sites, as indicated by saturation binding of [3H]DAMGO. The kappa and delta receptors represent approximately 10 +/- 3% and approximately 5 +/- 2% of the [3H]diprenorphine binding sites, respectively. Preexposure of neurons to 10 microM naloxone for 48 hr up-regulated the receptors by 40%, whereas incubation with 100 nM to 10 microM DAMGO for 48 hr resulted in a significant decrease in the Bmax value of opioid receptors, with a maximum reduction of 70%. The identification of a high level of opioid receptors expressed in isolated sensory neurons and their modulation by opioids demonstrates that cultured sensory neurons are an excellent model with which to study opioid receptor regulation.     

Electrophysiological and ultrasonic correlates of reproductive behavior in the male rat.

Monitored the ultrasonic vocalizations of 13 male Long-Evans rats and determined the correlation of these vocalizations with electrophysiological activity measured by chronically implanted hippocampal and cortical electrodes during mating with a female rat. Hippocampal theta rhythms were significantly correlated with high activity, mounting, intromissions, and preejaculatory excitatory behavior and were also significantly associated with 50-kHz short ultrasonic vocalizations. Postmount or postintromission behaviors (grooming, exploration) were closely correlated with an absence of ultrasonic vocalizations and the onset of irregular low-amplitude hippocampal EEG recordings. Long 22-kHz vocalizations occurred during the postejaculatory refractory period. Shorter 22-kHz vocalizations occurred during mating and were associated with unsuccessful intromissions or mounting attempts. Postejaculatory long 22-kHz vocalizations were significantly associated with irregular high-amplitude hippocampal EEG tracings, while preejaculatory short 22-kHz vocalizations were also accompanied by sleeplike irregular high-amplitude hippocampal EEG tracings with cortical spindling. Findings suggest that ultrasonic vocalizations are indicators of the sexual arousal of mating rats. (14 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)