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.     

Stimulation of the medial preoptic area facilitates sexual behavior but does not reverse sexual satiation.

The aim of the present study was to establish whether electrical and/or drug stimulation of the medial preoptic area/anterior hypothalamus (mPOA/AH) surmounts the sexual behavior inhibition that results from copulation to exhaustion. Thus, intermittent electrical stimulation of the mPOA/AH (alone or combined with the systemic injection of yohimbine or apomorphine, at doses that were subthreshold for reversing sexual exhaustion) or intrapreoptic treatments to block GABAergic transmission were applied to sexually satiated rats. The results suggest that the mPOA/AH is not responsible for male sexual behavior inhibition or for the pharmacologically induced sexual behavior expression in satiated rats. Data are discussed in terms of the roles ascribed to the mPOA/AH, both in the control of sexual behavior expression and in the regulation of the postejaculatory interval. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dorsolateral connections of the medial preoptic area and maternal behavior in rats.

The lateral connections of the medial preoptic area (MPOA) are essential for maternal behavior in rats. The purpose of this study was to more exactly specify the nature of this pathway. Exp 1 found that knife cuts that severed the dorsolateral connections of the MPOA were as effective as complete cuts in disrupting maternal behavior, whereas knife cuts that severed the ventrolateral MPOA connections were ineffective. These results suggest that MPOA efferents and afferents critical for maternal behavior leave or enter the MPOA dorsolaterally. Exp 2 located possible sources of critical afferent input. Lactating rats received MPOA lateral cuts with a horseradish peroxidase (HRP)-coated wire knife. Full lateral cuts and dorsolateral cuts disrupted maternal behavior and labeled more cells with HRP in the nucleus of the solitary tract and the locus coeruleus than did ventrolateral cuts, which did not disrupt maternal behavior. (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)     

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)     

Neonatal treatment with tamoxifen causes immediate alterations of the sexually dimorphic nucleus of the preoptic area and medial preoptic area in male rats

We have characterized two different types of Cl- currents in calf pulmonary artery endothelial (CPAE) cells by using a combined patch-clamp and Fura-2 microfluorescence technique to measure simultaneously ionic currents and the intracellular Ca2+ concentration, [Ca2+]i. Exposure of CPAE cells to 28% hypotonic solution induces cell swelling without a change in membrane capacitance and [Ca2+]i, and concomitantly activates a current. This current, I(Cl, vol), is closely correlated with the changes in cell volume and shows a modest outward rectification. It slowly inactivates at potentials more positive than +60 mV but is time- and voltage-independent at other potentials. Increase in [Ca2+]i by different maneuvers, such as application of vasoactive agonists (ATP), ionomycin, or loading of the cells directly with Ca2+ also activates a Cl- current, I(Cl, Ca). This current slowly activates at positive potentials, inactivates quickly at negative potentials and shows strong outward rectification. A time-independent component of the current activated by elevation of [Ca2+]i alone can be inhibited by cell shrinking by exposing the cells to hypertonic solution, indicating that an increase in [Ca2+]i also co-activates I(Cl, vol). Forskolin or cAMP never activated a current in CPAE cells, which indicates the lack of cAMP-activated channels in these cells. There is also no evidence for the existence of voltage-gated Cl- channels in resting, nonstimulated cells. Challenging a cell with elevated [Ca2+]i and hypotonic solutions activated I(Cl, vol) on top of I(Cl, Ca), suggesting that I(Cl, Ca) and I(Cl, vol) are different channels. We conclude that CPAE cells do not express voltage-gated (ClC-type) or cAMP-gated (CFTR-type) Cl- channels, but activate large Cl- currents after volume (mechanical?) or chemical (Ca2+) stimulation.     

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)     

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)     

Effects of neurochemical lesions of the preoptic area on male sexual behavior in the Japanese quail

Two experiments were carried out during which the noradrenergic neurotoxin, 5-amino-2,4-dihydroxy-alpha-methylphenylethylamine (5-ADMP) was applied to the brain of quail in order to evaluate the role of the noradrenergic system in the control of male copulatory behavior. In the first experiment, the ICV injection of 5-ADMP slightly enhanced the sexual behavior observed in testosterone (T)-treated castrated male quail. This brings additional support to the notion that norepinephrine tonically inhibits male copulatory behavior in quail. In the second experiment, 5-ADMP implanted directly into the preoptic area disrupted the restoration by T of copulatory behavior in castrated quail and, at the same time, produced a brain lesion that partly destroyed the sexually dimorphic medial preoptic nucleus, a previously established site of T action on behavior. These lesions produced by a high (presumably too high) concentration of neurotoxin provided an independent confirmation of effects previously observed after electrolytic lesions. Correlation analyses also confirmed that the medial part of the POM just rostral to the anterior commissure is more closely associated with copulatory behavior and may, therefore, represent a key center for steroid action on this behavior.     

8-OH-DPAT influences extracellular levels of serotonin and dopamine in the medial preoptic area of male rats

The effect of phospholipase C treatment on cardiolipin biosynthesis was investigated in intact H9c2 cardiac myoblasts. Treatment of cells with phosphatidylcholine-specific Clostridium welchii phospholipase C reduced the pool size of phosphatidylcholine compared with controls whereas the pool size of cardiolipin and phosphatidylglycerol were unaffected. Pulse labeling experiments with [1,3-3H]glycerol and pulse-chase labeling experiments with [1,3-3H]glycerol were performed in cells incubated or pre-incubated in the absence or presence of phospholipase C. In all experiments, radioactivity incorporated into cardiolipin and phosphatidylglycerol were reduced in phospholipase C-treated cells with time compared with controls indicating attenuated de novo biosynthesis of these phospholipids. Addition of 1,2-dioctanoyl-sn-glycerol, a cell permeable 1,2-diacyl-sn-glycerol analog, to cells mimicked the inhibitory effect of phospholipase C on cardiolipin and phosphatidylglycerol biosynthesis from [1,3-3H]glycerol indicating the involvement of 1,2-diacyl-sn glycerol. The mechanism for the reduction in cardiolipin and phosphatidylglycerol biosynthesis in phospholipase C-treated cells appeared to be a decrease in the activities of phosphatidic acid:cytidine-5'triphosphate cytidylyltransferase and phosphatidylglycerolphosphate synthase, mediated by elevated 1,2-diacylsn-glycerol levels. Upon removal of phospholipase C from the incubation medium, phosphatidylcholine biosynthesis from [methyl-3H]choline was markedly stimulated. These data suggest that de novo phosphatidylglycerol and cardiolipin biosynthesis may be regulated by 1,2-diacyl-sn-glycerol and support the notion that phosphatidylglycerol and cardiolipin biosynthesis may be coordinated with phosphatidylcholine biosynthesis in H9c2 cardiac myoblast cells.     

Appetitive sexual behavior in male rats: 2. sexual reward and level-changing behavior

The immunodeficiency of patients with chronic renal failure (CRF) is related to multiple and complex alterations of the cytokine network and of its target cells such as T or B lymphocytes, monocytes, fibroblasts or endothelial cells. Chronic activation of monocytic functions is recognized as a key factor in these immunological disorders. Since macrophage colony stimulating factor (M-CSF) is essential for the activation of several functions of monocytes and macrophages and their production of cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor alpha, we investigated its involvement in patients with CRF. When measured by ELISA, M-CSF serum levels were significantly higher in patients with progressive CRF and those on hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) than in controls. M-CSF serum levels did not correlate with the degree of renal insufficiency and were probably related to complex alterations in its production and/or degradation by the specific M-CSF receptors of macrophages. In HD patients the M-CSF serum concentrations inversely correlated with the number of circulating lymphocytes and were significantly higher in anemic patients requiring treatment with erythropoietin. Our results suggest that M-CSF may play a role in altering the immune system in uremic patients by maintaining in the circulation and tissues permanently primed monocytes and/or macrophages that can then be triggered to an activated state by secondary stimuli such as endotoxins, complement components, other cytokines or contact with foreign surfaces.     

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)     

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.     

Dopamine release in the medial preoptic area is related to hormonal action and sexual motivation.

To help elucidate how general the role of dopamine (DA) release in the medial preoptic area (mPOA) is for the activation of male sexual behavior in vertebrates, we recently developed an in vivo microdialysis procedure in the mPOA of Japanese quail. Using these techniques in the present experiment, the temporal pattern of DA release in relation to the precopulatory exposure to a female and to the expression of both appetitive and consummatory aspects of male sexual behavior was investigated. Extracellular samples from the mPOA of adult sexually experienced male quail were collected every 6 min before, while viewing, while in physical contact with, and after exposure to a female. In the absence of a precopulatory rise in DA, males failed to copulate when the barrier separating them from the female was removed. In contrast, males that showed a substantial increase in mPOA DA during precopulatory interactions behind the barrier, copulated with females after its removal. However, there was no difference in DA during periods when the quail were copulating as compared to when the female was present but the males were not copulating. In addition, we show that precopulatory DA predicts future DA levels and copulatory behavior frequency. Furthermore, the size of the cloacal gland, an accurate indicator of testosterone action, is positively correlated with precopulatory DA. Taken together, these results provide further support for the hypothesis that DA action in the mPOA is specifically linked to sexual motivation as compared to copulatory behavior per se. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of rostral medial forebrain bundle and olfactory tubercle lesions upon sexual behavior of male rats.

Examined the effect on sexual behavior of 57 male Sprague-Dawley rats of reduced olfactory system input to the preoptic area and medial forebrain bundle (MFB). Bilateral electrolytic lesions in the MFB just caudal to the preoptic area virtually abolished mating behavior. Electrolytic lesions or sham lesions placed bilaterally in the olfactory tubercle produced decrements in the mating behavior. There was no evidence of gonadotropic dysfunction in any of the groups, nor were there significant differences in their mean body weights at sacrifice. (22 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of sexually dimorphic medical preoptic area of the hypothalamus in the sexual behaviour of male and female rats

The human placental alkaline phosphatase (PLAP) gene was analysed for its utility as a histochemically detectable reporter gene in transgenic mice. A reporter gene was made by linking the PLAP structural gene to an enhancer-promoter element from the human beta-actin gene. This gene was inserted into the mouse genome by transfection of embryonic stem cells, and by microinjection of fertilized eggs. Histochemical staining showed that the transgene was uniformly expressed in four of four stable ES cell lines, and in all ten tissues examined from adult animals from five lines of transgenic mice. Non-transgenic cells did not stain. These results suggest that the human PLAP gene will be of utility in studies requiring phenotypic marking of cells in tissues of mice.     

Sleep induction by microinjection of pentobarbital into the medial preoptic area in rats

In a previous study we have shown that microinjection of the benzodiazepine hypnotic triazolam into the medial preoptic area increases sleep in rats. In order to determine whether this effect is specific to benzodiazepines, or whether it occurs with hypnotic medications from other pharmacologic classes, we have microinjected pentobarbital (1 and 100 micrograms) and vehicle in random sequence into rats and performed two hour sleep studies in the daytime with the lights on. Both doses significantly decreased sleep latency and increased nonREM and total sleep. The amount of REM sleep, REM latency, and intermittent waking time were not significantly altered. These data are consistent with the hypothesis that the medial preoptic area may be involved in sleep induction by both benzodiazepine and barbiturate hypnotic medications.     

Studies of instrumental behavior with sexual reinforcement in male rats (Rattus norvegicus): II. Effects of preoptic area lesions, castration, and testosterone.

We studied effects of lesions to the medial preoptic area (POA), castration, and testosterone replacement on instrumental and unconditioned sexual behavior in male rats. We achieved instrumental measures of sexual motivation by training males to work for an estrous female, presented in an operant chamber under a second-order schedule of reinforcement. POA lesions abolished mounts, intromissions, and ejaculation but did not disrupt instrumental responses, investigation of the female, or abortive mounting attempts. Castration abolished attempts to copulate and also caused a marked decrease in instrumental responses. Testosterone resulted in the prompt reinstatement of instrumental responses and more gradual recovery of unconditioned sexual behavior. We discuss these results in terms of the motivational and performance effects of these neuroendocrine manipulations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)