Role of the medial preoptic area/anterior hypothalamus in the control of masculine sexual behavior.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
R G Paredes
Publications and source records attributed to R G Paredes.
Neurogenesis and cell migration into the sexually dimorphic preoptic area/anterior hypothalamus of the fetal ferret.
A sexually dimorphic male nucleus (MN) of the preoptic area/anterior hypothalamus (POA/AH), comprising large, estradiol-receptor containing neurons, is formed in male ferrets due to the action of estradiol, derived from the neural aromatization of circulating testosterone, during the last quarter of a 41-day gestation. Two experiments were conducted to compare the birthdates and the migration pattern of cells into the sexually dimorphic portion of the dorsomedial POA/AH as well as the nondimorphic ventral nucleus (VN) of the POA/AH of males and females. In experiment 1 the thymidine analog, bromodeoxyuridine (BrdU), was injected into the amniotic sacs of fetuses of different mothers between embryonic (E) days 18 and 30. Kits from all mothers were sacrificed on E38, and brains were processed to localize BrdU immunoreactivity (IR) for determining the birthdates of neurons in the POA/AH. Cells in the MN-POA/AH of males and in a comparable region of females were born between E22 and E28; cells in the nondimorphic VN-POA/AH of both sexes were born between these same ages. These results suggest that cells in the sexually dimorphic as well as the nondimorphic subdivision of the ferret POA/AH are born during the same embryonic period. This is well before the ages (E30-E41) when administering testosterone to females can stimulate, and blocking androgen aromatization in males can inhibit, MN-POA/AH differentiation. In experiment 2 BrdU was injected on E24, and kits from different litters were perfused on E30, E34, or E38. Brains were processed for BrdU-IR as well as glial fibrillary acidic protein (GFAP), which served as a marker for radial glial processes. The orientation of radial glial processes in fetal brains of both sexes suggested that cells migrate into the dorsomedial POA/AH from proliferative zones lining the lateral as well as the third ventricles. Quantitative, computer-assisted image analysis of BrdU-IR in groups of male and female brains supported this hypothesis. There were no significant sex differences in the distribution of BrdU-IR over the three ages studied, suggesting that formation of the MN-POA/AH in males cannot be attributed to an effect of estradiol on the migration of those cells born on E24 into this sexually dimorphic structure. Finally, total BrdU-IR did not change significantly in the POA/AH of male and female kits killed at E30, E34, or E38 while the area of the POA/AH increased more than 2.5-fold over this period, suggesting that few of the POA/AH cells born on E24 die during this period in either sex. In the absence of evidence that formation of the male ferret's MN-POA/AH depends on steroid-induced changes in neurogenesis, cell migration, or death, we suggest that the specification of a particular neuronal phenotype (e.g., large somal size; capacity to produce some undetermined neurotransmitter or neuropeptide) may be responsible.
Animals↗
Estrogenic control of preoptic area development in a carnivore, the ferret.
1. Evidence is reviewed which shows that a sexually dimorphic nucleus located in the dorsomedial portion of the male ferret's preoptic area/anterior hypothalamus (POA/AH), called the male nucleus of the POA/AH (Mn-POA/AH), develops during fetal life in response to the action of estradiol, which is formed directly in the nervous system from circulating testosterone over the final quarter of a 41-day gestation. 2. Results are summarized which establish that neurons which make up the Mn-POA/AH are born prior to the critical period of estradiol's action in the male brain. Other data show that some radial glial processes, visualized immunocytochemically using antibodies against GFAP, emanate from proliferative zones at the base of the lateral ventricles in a dorsal-ventral orientation, whereas other glial processes emanate laterally from proliferative zones lining the third ventricle. 3. We suggest that at least some neurons which constitute the dorsomedial POA/AH are born in proliferative zones surrounding the lateral ventricles, raising the question of whether estradiol acts in developing males to influence the migration of these neurons along radial glial guides into the Mn-POA/AH. 4. Finally, evidence is summarized showing that excitotoxic lesions of the dorsomedial POA/AH enhance males' preference to approach and interact with another sexually active male, as opposed to an estrous female, when adult subjects are castrated and treated with estradiol benzoate. These data suggest that the sexually dimorphic Mn-POA/AH is an essential part of a CNS circuit which determines heterosexual partner preference in the male ferret.
Animals↗
Dopamine and sexual behavior in the male rabbit.
Male rabbits were treated with the dopamine releasing drug amphetamine or the dopamine D1/D2 receptor antagonist cis(Z)-flupenthixol. Amphetamine, 1 to 4 mg/kg, had no effect on sexual behavior. Flupenthixol, 2 mg/kg, reduced the proportion of rabbits that ejaculated and the number of ejaculations per test. Lower doses were ineffective. Castrated males were treated with both drugs at two intervals after castration, 19-21 and 27-29 days postcastration, respectively. Amphetamine was without effect while flupenthixol, 1 mg/kg, reduced sexual behavior at the test 19-21 days postcastration. At the second test, sexual behavior was almost completely absent in control animals. Therefore, no further reduction could be observed after treatment with flupenthixol. Another group of animals was castrated and given androgen replacement. Testosterone decanoate was injected once weekly at a dose of 3 mg/kg. This treatment maintained a stable, low sexual activity. In these animals, amphetamine was again ineffective whereas flupenthixol, 1 mg/kg, inhibited sexual behavior. Gross motor function was evaluated in a water escape test. Amphetamine was inactive, and the effective dose of flupenthixol was 10 mg/kg. This dose is far above the dose required for inhibiting sexual behavior. In sum, facilitated dopaminergic transmission does not seem to affect on sexual behavior in the male rabbit, whereas reduced dopaminergic activity disrupts this behavior.
Animals↗
Telencephalic and diencephalic origin of radial glial processes in the developing preoptic area/anterior hypothalamus.
Neuronal birth-dating studies using [3H] thymidine have indicated that neurons in the preoptic area/anterior hypothalamus (POA/AH) are derived primarily from progenitors in proliferative zones surrounding the third ventricle. Radial glial processes are potential guides for neuronal migration, and their presence and orientation during development may provide further information about the origin of cells in the POA/AH. In addition to determining the orientation of radial glial fibers, we examined the relationship of neurons with identified birth dates to radial glial processes in the developing POA/AH of ferrets. Neuronal birth dates were determined by injecting ferret fetuses with bromodeoxyuridine (BrdU) at several different gestational ages; brains were taken from ferret kits at subsequent prenatal ages. Sections were processed for immunocytochemistry to reveal vimentin or glial fibrillary acidic protein in radial glial, or BrdU-labeled cell nuclei. Numerous radial glial processes extended from the lateral ventricles through ventral portions of the septal region to the pial surface of the POA/AH. These fibers both encapsulated and coursed ventrally through and around the anterior commissure of ferret, rat, and mouse fetuses. These ventrally directed fibers were less evident at older ages. In double-labeled sections from ferrets, BrdU-labeled cells in the dorsal POA/AH were often aligned in the same dorsal-ventral orientation as adjacent radial glial fibers. We suggest that a subset of neurons, originating in telencephalic proliferative zones, migrates ventrally along radial glial guides into the dorsal POA/AH.
Animals↗
A sex comparison of increments in FOS immunoreactivity in forebrain neurons of gonadectomized, testosterone-treated rats after mounting an estrous female.
The protein product of the immediate-early gene, c-fos, was visualized immunocytochemically in forebrain neurons of gonadectomized male and female rats which were injected daily with testosterone propionate (TP) and either tested for mounting directed toward a sexually receptive female or left alone in a test arena. Lidocaine anesthetic paste was applied to the genital region of all subjects in an attempt to reduce the incidence of intromissive behavior patterns. In this way we hoped to compare the relative contribution in the two sexes of vomeronasal/olfactory, as opposed to genital/somatosensory, stimuli to mounting-induced forebrain Fos immunoreactivity (FOS-IR). Males displayed high levels of mounting, with very few intromissions; females displayed a similar level of mounting coupled with a significantly higher number of intromissive behavior patterns than males. Significant increments in the number of FOS-IR neurons were seen in the medial amygdala (mAMYG) and medial preoptic area (mPOA) of males and females killed 1 h after testing. In experiment 2, ovariectomized, TP-treated females were given a unilateral lesion of the olfactory peduncle and subsequently tested with an estrous female as in Experiment 1. Unilateral lesions significantly reduced the number of FOS-IR neurons counted in the ipsilateral piriform (primary olfactory) cortex, but failed to attenuate the ability of stimuli associated with mounting an estrous female to augment FOS-IR in ipsilateral mAMYG or mPOA neurons. The results suggest that vomeronasal/olfactory stimuli were primary determinants of the mounting-induced increments in neuronal FOS-IR observed in males, whereas in females a combination of genital/somatosensory and olfactory/vomeronasal stimuli account for the observed induction of forebrain FOS-IR.
Amygdala↗
The GABAB antagonist CGP 35348 inhibits the effects of baclofen on sexual behavior and motor coordination.
The intraperitoneal injection of 100 mg/kg of CGP 35348 completely blocked the effects of 2.5 mg/kg of (R)-baclofen on sexual behavior and motor coordination in male rats. Doses of 50 and 25 mg/kg partially blocked the effects of (R)-baclofen on sexual behavior but not those on motor coordination. The antagonist itself had no effect on these behaviors. These observations confirm previous data suggesting that the inhibitory effect of (R)-baclofen on sexual behavior is not only a consequence of motor deficiencies and indicates that this effect is due to an action at GABAB receptors. The lack of effect of CGP 35348 on sexual behavior when the drug was administered alone may suggest that GABAB receptors are not important for the physiological control of sexual behavior.
Animals↗
Altered sexual partner preference in male ferrets given excitotoxic lesions of the preoptic area/anterior hypothalamus.
Numerous experiments suggest that perinatal exposure of male vertebrates to testosterone (T), or its estrogenic metabolites, masculinizes aspects of coital function, including males' characteristic preference to seek out and mate with a female as opposed to another male conspecific. Other research has shown that this perinatal action of sex steroids also masculinizes aspects of neuronal morphology in the medial preoptic area/anterior hypothalamus (mPOA/AH). We asked whether neurons of the mPOA/AH contribute to males' preference to mate with a female. The ferret is an ideal species in which to ask this question. When tested in a T-maze after gonadectomy and treatment with estradiol benzoate (EB), female ferrets prefer to approach and receive neck grips from a stimulus male whereas males prefer to approach and neck grip an estrous female. In the minority of trials when EB-treated males approach a stimulus male, they occasionally receive a neck grip to which they display receptive postures as opposed to agonistic behaviors. In Experiment 1 castrated, EB-treated male ferrets which received bilateral infusions of the NMDA excitotoxin, quinolinic acid aimed at the dorsomedial POA/AH, preferred to approach a stimulus male significantly more often than groups of control males which either received a sham lesion, received a unilateral mPOA/AH lesion or in which bilateral infusions of quinolinic aci produced no histologically detectible excitotoxic damage to the mPOA/AH. Males with bilateral mPOA/AH lesions also displayed neck gripping on a significantly lower percentage of trials than control males when they approached the stimulus female. Ovariectomized, EB-treated female ferrets with bilateral mPOA/AH lesions, like control females, preferred to approach and receive neck grips from a stimulus male. The males used in Experiment 1 had never experienced circulating levels of T characteristic of the breeding season. Therefore, in Experiment 2 prepubertally gonadectomized males and females were treated chronically with a high dose of T propionate (TP) and tested several times with a receptive female prior to brain surgery. Males which received bilateral excitotoxic lesions of the mPOA/AH neck gripped and mounted stimulus females significantly less than control males. Again, when given EB followed by T-maze tests of partner preference, males with bilateral mPOA/AH lesions, like sham-operated female controls, preferred to approach the sexually active stimulus male significantly more often than control males, which preferred to approach the stimulus female. Our results suggest that neurons in the mPOA/AH play an important role in the integration of sensory cues which determine heterosexual partner preference in the male ferret, in addition to facilitating masculine coital performance.
Animals↗
Differential effects of the serotonin1A agonist, 8-OH-DPAT, on masculine and feminine sexual behavior of the ferret.
Administration of the serotonin (5-HT)1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) facilitates the expression of masculine sexual behavior in male and female rats as well as in male rhesus monkeys and inhibits lordosis behavior in female rats. In the present study the effects of 8-OH-DPAT on masculine coital and feminine proceptive and receptive behaviors were evaluated in the ferret, a carnivore. Doses of 8-OH-DPAT (0.1 or 0.2 mg/kg) that facilitate masculine sexual behavior in rats inhibited masculine sexual behavior in castrated, estradiol benzoate (EB)-treated male ferrets. Lower doses of 8-OH-DPAT (5 or 10 micrograms/kg) had no effect on the expression of masculine sexual behavior in either males or females. In contrast to the female rat, administration of 8-OH-DPAT significantly facilitated receptive behaviors in ovariectomized, EB-treated female ferrets. None of the doses of 8-OH-DPAT tested modified proceptive behaviors of gonadectomized, EB-treated male or female ferrets, as assessed in a T-maze in which the subjects could choose to approach either a castrated, sexually inactive male or a castrated, testosterone-primed stud male. Thus whereas the 5-HT1A receptor agonist 8-OH-DPAT facilitates masculine sexual behavior and inhibits lordosis in the rat, it inhibits masculine sexual behavior and facilitates receptivity in the ferret. The different effects of 8-OH-DPAT observed in these two species may reflect differences in the neural control of their masculine coital and feminine receptive responses, respectively.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Opioids and sexual behavior in the male rabbit: the role of central and peripheral opioid receptors.
The purpose of the present series of experiments was to analyze the effects of morphine and naloxone on sexual behavior in the male rabbit, and to evaluate the role of central and peripheral opioid receptors. Morphine was found to inhibit sex behavior in a dose dependent way. The effects were slight at 5 min postinjection. At 1 hr all aspects of sexual behavior were reduced. This effect lasted at least until 3 hrs postinjection. Subcutaneous (s.c.) injection produced effects at lower doses than intraperitoneal (i.p.) injection. Minimal effective doses were 1.25 and 5 mg/kg, respectively. Naloxone also inhibited sexual behavior. Again, s.c. administration had effects at lower doses than i.p. administration (0.25 vs 16 mg/kg). The effects of morphine were reduced but not completely antagonized by several doses of naloxone, independently of whether s.c. or i.p. administration were used. An opioid kappa agonist, bremazocine, inhibited sexual behavior at a low dose (30 micrograms/kg). It is suggested that the inhibitory effects of morphine may be mediated by the kappa receptor. A peripheral opioid antagonist, methylnaloxone, had no effects by itself and was unable to modify the effects of morphine. It is concluded that the effects of morphine are localized within the central nervous system. This is further supported by the observation that loperamide, a peripheral opiate agonist, had only marginal effects on sex behavior.
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
Hypothalamic but not cortical grafts induce recovery of sexual behavior and connectivity in medial preoptic area-lesioned rats.
We have previously shown that hypothalamic fetal brain grafts induced recovery of sexual behavior in medial preoptic area (MPOA)-lesioned male rats. In the present series of experiments, male rats with completely abolished sexual behavior by MPOA lesions received either hypothalamic or frontal cortical fetal grafts. The animals that received hypothalamic grafts showed a gradual recovery of sexual behavior. In contrast, those animals who received cortical grafts did not recover sexual behavior during the 15 weeks after the graft. In addition, to evaluate the connectivity of the grafted tissue with the host brain, a retrograde tracer, fluorogold, was injected in the dorsal tegmental area. Fluorogold-labeled cells were found in the hypothalamic, but not in the cortical grafts. These results suggest that specificity of the grafted tissue and connectivity between brain grafts and host tissue are necessary for the recovery of male sexual behavior in MPOA-lesioned rats.
Animals↗
Socio-sexual behavior in male rats after lesions of the medial preoptic area: evidence for reduced sexual motivation.
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.
Animals↗
Electromyographic activity of rat ischiocavernosus muscles during copulation after treatment with a GABA-transaminase inhibitor.
The administration of GABA-transaminase inhibitors (GABA-TIs) to male rats reduces the proportion of mounts that result in intromissions. Copulatory pelvic thrusting remains normal, despite the fact that animals treated with GABA-TIs show gross deficiencies in other motor acts. In order to determine whether altered sexual behavior produced by GABA-TI could be due to deficiencies in activity of striated penile muscles, we recorded the electromyographic (EMG) activity of the ischiocavernosus (IC) muscle during copulation in male rats treated with sodium valproate. The duration of IC EMG bursts was reduced by sodium valproate in separate tests that allowed or prevented intromission. There was no effect on EMG amplitude or frequency. It is suggested that insufficient activity of the IC muscles reduces the likelihood of vaginal penetration. The actions of GABA may be localized to hypothalamic or brain stem nuclei with GABAergic projections to the spinal motoneurons controlling the IC muscles, or GABA may act directly on these neurons.
4-Aminobutyrate Transaminase↗
Sexual behavior enhances postictal behavioral depression in kindled rats: opioid involvement.
Past research has demonstrated brain opioid and GABA release in response to ejaculation. In the present study we evaluated the potential role of these neurotransmitters in the postictal behavioral depression (PBD), after-discharge (AD) duration, and seizure intensity in rats kindled in the medial preoptic area (MPOA) and amygdala (AMG). The PBD, the AD duration and the seizure intensity were measured after a standard kindling stimulus and after a standard kindling stimulus applied 2 min after ejaculation. The PBD was significantly increased when the animals were stimulated 2 min after ejaculation. This increase was found in MPOA- but not in AMG-kindled rats. Ejaculation had no effect on AD duration or seizure intensity. Naloxone administration before the initiation of sexual behavior completely blocked the increase in PBD in MPOA-kindled rats. It is suggested, by indirect evidence, that opioid release during sexual behavior is added to the release associated with kindled seizures, increasing the duration of the PBD. Since sexual behavior lacked effect on AD duration or seizure intensity, no evidence could be found suggesting that functionally relevant amounts of GABA are released during this behavior.
Amygdala↗
Facilitation of sexual behavior shortly after electrolytic lesion of the medial preoptic area: what does it mean?
To analyze the behavioral effects of an unphysiological manipulation of the medial preoptic area (MPOA), sexually experienced male rats received small bilateral electrolytic lesions within this area. Thirty-five percent of the lesioned animals showed a drastic facilitation of sexual behavior when tested 3 h after lesion. The number of intromissions, ejaculation latency, and postejaculatory interval were drastically reduced. The mean number of ejaculations was significantly higher in lesioned animals that displayed the behavior in comparison both to an intact group and a sham-lesioned group. Neither the size of the lesion nor its exact location could be correlated with the facilitation of sexual behavior. However, animals that showed facilitation tended to have the lesion located in the ventral part of the MPOA. Lesions rostral or dorsal to the MPOA were ineffective. It is suggested that the small electrolytic lesions in the MPOA produced iron deposits that stimulated the remaining intact preoptic region, resulting in the drastic facilitation of sexual behavior. The results of the present study support the hypothesis suggesting that the MPOA is involved in the mechanisms related to the initiation and execution of sexual behavior.
Animals↗
GABA and behavior: the role of receptor subtypes.
The discovery of different GABA receptor subtypes has stimulated research relating this neurotransmitter to a variety of behavioral functions and clinical disorders. The development of new and specific GABAergic compounds has made it possible to try to identify the specific functions of these receptors. The purpose of the present review is to evaluate the data regarding the functions of the GABA receptor subtypes in different behaviors such as motor function, reproduction, learning and memory, and aggressive-defensive behaviors. A description of GABAergic functions (stress, peripheral effects, thermoregulation) that might directly or indirectly affect behavior is also included. The possible involvement of GABA in different neurological and psychiatric disorders is also discussed. Although much research has been done trying to identify the possible role of GABA in different behaviors, the role of receptor subtypes has only recently attracted attention, and only preliminary data are available at present. It is therefore evident that still much work has to be done before a clear picture of the behavioral significance of these receptor subtypes can be obtained. Nevertheless, existing data are sufficient to justify the prediction that GABAergic agents, in the near future, will be much used in the field of behavioral pharmacology. It is hoped that the present review will contribute to this. Some specific suggestions concerning the most efficient way to pursue future research are also made.
Animals↗
Fetal brain transplants induce recovery of male sexual behavior in medial preoptic area-lesioned rats.
Male rats received bilateral lesions within the medial preoptic area which completely abolished sexual behavior. Hypothalamic fetal brain transplants gradually restored sexual behavior to prelesion levels by the 6th week after the transplant. Immunocytochemical analyses revealed tyrosine hydroxylase immunoreactivity neurons within the transplanted tissue. These results demonstrate that fetal brain transplants can restore an innate complex behavior in which no spontaneous recovery is observed.
Animals↗