Permanent changes in sexual behavior induced by medial preoptic area kindling-like stimulation

Kindling is a model of neuronal plasticity in which repeated electrical stimulation of certain brain areas leads to the progressive development of motor seizures. We have previously shown that medial preoptic area (MPOA) kindling induces sexual behavior in non-copulating male rats. In the present experiment, we found that previously non-copulating male rats display sexual behavior even 8 months after kindling stimulation had ceased. In addition, elicitation of an afterdischarge (AD) or stimulation until an intermediate stage was sufficient to induce sexual behavior in previously non-copulating male rats. These results suggest that kindling like stimulation, without seizure development, can induce permanent behavioral changes.     

A functional medial preoptic nucleus (MPO) is required for scrotal thermal stimuli to alter the neuronal activity of thermoresponsive ventromedial hypothalamic (VMH) neurons

Thermoresponsiveness of ventromedial hypothalamic (VMH) neurons to scrotal thermal stimulation was determined before and after microinjection of lidocaine into the medial preoptic nucleus (MPO). Male, urethane anesthetized Sprague-Dawley rats, maintained colonically at 37 °C had VMH extracellular neuronal activity recorded following 3 cycles of scrotal thermal stimulation (localized, incremental heating and cooling, between 10 and 40 °C). Based on their thermal coefficients (TC), warm (WRN), cold (CRN) thermoresponsive and temperature non-responsive (TNRN) VMH neurons had their neuronal activity recorded following each cycle of scrotal thermal stimulation before and after MPO injections of sterile saline (300 nl volume) or 2% buffered lidocaine (200 ng). Thermoresponsiveness of all warm and cold VMH neurons to scrotal thermal stimulation was blocked by prior lidocaine administration into the MPO, effects that were reversed ~ 60 min after. However, MPO lidocaine administration caused no significant change in the thermal coefficients of VMH TNRNs to scrotal thermal stimulation. Results infer that a functional MPO is required for thermal afferent signals arising from the scrotum to reach thermoresponsive VMH neurons.     

Effects of discrete lesions of the sexually dimorphic nucleus of the preoptic area or other medial preoptic regions on the sexual behavior of male rats

The sexually dimorphic nucleus of the rat medial preoptic area (SDN-POA) has a volume five times larger in the adult male compared with that of the adult female. In the present study, the effects of discrete electrolytic destruction of the SDN-POA or other specific medial preoptic (MPOA) regions on masculine sexual behavior were determined in adult, sexually experienced male rats. Small lesions encompassing the SDN-POA had no effect on the maintenance of copulatory behavior. Lesions of similar size placed within the ventral or anterio-dorsal MPOA also did not consistently affect the display of masculine sexual behavior. However, animals that received small lesions within their dorsal MPOA showed a substantial, long-term decrease in number of mounts, intromissions, and ejaculations compared to these parameters in sham-lesioned control rats, thus indicating a lesion-induced disruption of those neural mechanisms mediating these behaviors. Collectively these data suggest that the SDN-POA is not critical for a full expression of male sexual behavior and that the dorsal MPOA may be more important than other MPOA regions for copulatory behavior.     

Paced mating behavior in the female rat following lesions of three regions responsive to vaginocervical stimulation

The present study examines the effects of ibotenic acid lesions of the medial amygdala, the bed nucleus of the stria terminalis and the medial preoptic area on the display of paced mating behavior in female rats. Lesions of either the medial amygdala or the bed nucleus of the stria terminalis have no effect on the display of paced mating behaviors in ovariectomized, hormone-primed rats. In contrast, lesions of the medial preoptic area significantly lengthen contact-return latencies following intromissions and ejaculations and increase withdrawal from the male following intromissions. The present study demonstrates that the medial amygdala and the bed nucleus of the stria terminalis are not involved in the behavioral responses accompanying paced mating behavior, whereas the medial preoptic area is a critical component of the neural circuit mediating paced mating behavior as well as other appetitive aspects of mating.     

The bisexual brain: sex behavior differences and sex differences in parthenogenetic and sexual lizards

The parthenogenetic lizard Cnemidophorus uniparens alternates in the display of male-like and female-like sexual behavior, providing a unique opportunity for determining the neuronal circuits subserving gender-typical sexual behavior within a single sex. Here we report a 6-fold greater [¹⁴C]2-fluoro-2-deoxyglucose uptake in the medial preoptic area of C. uniparens displaying male-like behavior in comparison with C. uniparens displaying female-like receptivity. The ventromedial nucleus of the hypothalamus showed greater 2DG accumulation in receptive C. uniparens than in courting C. uniparens. When a related sexual species (C. inornatus) was compared to the unisexual species, the anterior hypothalamus in C. inornatus males exhibited significantly greater activity.     

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.     

Stimulation of the medial amygdala enhances medial preoptic dopamine release: implications for male rat sexual behavior

Increased dopamine (DA) in the medial preoptic area (MPOA) facilitates male sexual behavior. A major source of innervation to the MPOA is the medial amygdala (MeA). We now report that chemical stimulation of the MeA enhanced levels of extracellular MPOA DA in anesthetized male rats. These results suggest that DA activity in the MPOA can be regulated by input from the MeA to the MPOA.     

Neural control of the daily rhythm of sexual behavior in the male golden hamster

Circadian and neural mechanisms important for the organization of reproductive behavior in the male golden hamster were examined. The sexual behavior of male hamsters exhibits diel variations; males are quicker to initiate copulation and to ejaculate in the dark phase than in the light phase of a daily light-dark cycle. The copulatory rhythm is endogenously generated and persists under constant environmental conditions. Destruction of the suprachiasmatic nuclei (SCN) eliminated the normal diurnal rhythm of sexual behavior without affecting copulation per se. In contrast to SCN lesion effects, damage to the medial preoptic area (MPOA) reduced or eliminated copulation; in those MPOA-ablated animals that continued to copulate, the circadian modulation of sexual behavior remained intact.     

Topography in the preoptic region: differential regulation of appetitive and consummatory male sexual behaviors

Several studies have suggested dissociations between neural circuits underlying the expression of appetitive (e.g., courtship behavior) and consummatory components (i.e., copulatory behavior) of vertebrate male sexual behavior. The medial preoptic area (mPOA) clearly controls the expression of male copulation but, according to a number of experiments, is not necessarily implicated in the expression of appetitive sexual behavior. In rats for example, lesions to the mPOA eliminate male-typical copulatory behavior but have more subtle or no obvious effects on measures of sexual motivation. Rats with such lesions still pursue and attempt to mount females. They also acquire and perform learned instrumental responses to gain access to females. However, recent lesions studies and measures of the expression of the immediate early gene c-fos demonstrate that, in quail, sub-regions of the mPOA, in particular of its sexually dimorphic component the medial preoptic nucleus, can be specifically linked with either the expression of appetitive or consummatory sexual behavior. In particular more rostral regions can be linked to appetitive components while more caudal regions are involved in consummatory behavior. This functional sub-region variation is associated with neurochemical and hodological specializations (i.e., differences in chemical phenotype of the cells or in their connectivity), especially those related to the actions of androgens in relation to the activation of male sexual behavior, that are also present in rodents and other species. It could thus reflect general principles about POA organization and function in the vertebrate brain.     

An HRP study of the afferent connections to rat medial hypothalamic region

Afferent connections to the medial hypothalamic region in the rat were studied using horseradish peroxidase (HRP). HRP was injected iontophoretically by a parapharyngeal approach. After HRP injections into the ventromedial hypothalamic nucleus, labeled cells were found mainly in the medial and basolateral amygdaloid nuclei, subiculum, peripeduncular nucleus and the parabrachial area. Labeled cells following HRP injections into the dorsomedial hypothalamic nucleus were found mainly in the lateral septal nucleus, nucleus accumbens, bed nucleus of the stria terminalis, pontine central gray and the parabrachial area. HRP-labeled cells following the medial preoptic area injections were found mainly in the infralimbic cortex, lateral and medial septal nuclei, nucleus accumbens, diagonal band, bed nucleus of the stria terminalis, medial amygdaloid nucleus, subiculum, peripedunclar nucleus and the parabrachial area. The intrahypothalamic connections were also discussed.     

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.     

Role of oxytocin in the hypothalamic regulation of sexual receptivity in hamsters

Oxytocin (OXT) has been implicated in the control of a variety of social and reproductive behaviors in several species. The purpose of the present study was to test the hypothesis that OXT activity within the medial preoptic-anterior hypothalamus (MPOA-AH) and the ventromedial hypothalamus (VMH) plays a critical role in the expression of sexual receptivity in Syrian hamsters. The first 2 experiments investigated whether OXT would stimulate sexual receptivity in female hamsters in a dose-dependent manner. A 3rd experiment investigated whether sexual receptivity would be inhibited when endogenous OXT activity was blocked. Microinjection of OXT into the MPOA-AH or the VMH induced sexual receptivity in a dose-dependent manner in ovariectomized (OVX) hamsters primed with estradiol. Microinjection of a selective OXT antagonist, d(CH₂)₅[Tyr(Me)²Thr⁴,Tyr-NH₂₉] ornithine vasotocin into the MPOA-AH or the VMH significantly reduced the levels of sexual receptivity exhibited by OVX hamsters administered estradiol and progesterone. These findings support the hypothesis that OXT activity in the MPOA-AH and the VMH plays an important role in the regulation of sexual receptivity in hamsters.     

Sagittal knife cuts in the far-lateral hypothalamus reduce sexual receptivity in female hamsters

We have previously shown that hypothalamic knife cuts confined to the sagittal plane lateral to the medial anterior hypothalamus-ventromedial nucleus can disrupt sexual receptivity in female golden hamsters. In the present study we have compared the effects of varying the lateral position of sagittal cuts located at this same rostral-caudal level. Near-lateral (NL) cuts were placed at or just lateral to the fornix, while far-lateral (FL) cuts were placed at the lateral edge of the medial forebrain bundle. Ovariectomized, estradiol benzoate plus progesterone-treated females were given weekly tests for lodosis before and after hypothalamic cuts. Changes in body weight and agonistic behavior were also recorded. Both NL and FL cuts reduced lordosis in response to both manual stimulation and a sexually active male. Postoperatively, it was more difficult to elicit lordosis from these females, and if elicited, the duration of the response was reduced. NL, but not FL, cuts also increased agonistic behavior, and produced obesity. Since both NL and FL cuts severed axons traveling in the region of the supraoptic commissures (SOC), these data support our hypothesis that these SOC connections are critical for sexual receptivity. The SOC carry both efferents and afferents of the ventromedial hypothalamus. Sagittal-plane cuts which interrupt the SOC may disrupt lordosis by cutting either or both types of connection.     

Medial preoptic and hypothalamic neuronal activity during sexual behavior of the male monkey

Neuronal activity changes in the medial preoptic area of the male monkey were related to the commencement of sexual behavior, penile erection and the refractory period following ejaculation.Increased neuronal activity in the dorsomedial hypothalamic nucleus was found to be synchronized to each mating act.The involvement of medial preoptic neurons in sexual arousal, initial penile erection and that of dorsomedial hypothalamic neurons in the copulatory act are suggested by the present findings.     

Effects of microiontophoretically applied chemicals on hypothalamic neural activity

The effects of lateral hypothalamic (LH) stimulation on ipsilateral lateral preoptic area (LPA) neuronal activity were determined in anesthetized rats. The effects of LPA stimulation on LH neuronal activity were also determined. Recordings from 99 hypothalamic neurons indicate that reciprocal inhibitory relations exists between the LPA and LH. Following single rectangular pulse, 0.5 msec, 0–500 μA, stimulation short latency decreases in activity occurred. Longer latency increases in activity were also observed. Dose response relations were established for 90% of the LPA neurons following LH stimulation and for 80% of the LH neurons following LPA stimulation. Decreases and in a few cases increases in activity seemed to involve only one or two synapses. Antidromic responses revealed relatively slow conduction velocities of 0.4–0.9 m/sec. Results demonstrate a considerable degree of interconnectivity between the LPA and LH along the extent of the medial forebrain bundle. In addition to establishing the nature of these interconnections, the cross validation between the horseradish peroxidase neuroanatomical technique and electrophysiological methods was discussed as a means of determining hypothalamic organization and function.     

Visual responses related to food discrimination in monkey lateral hypothalamus during operant feeding behavior

Single neuron activity was recorded from monkey lateral hypothalamic area (LHA) to relate neuronal events to food discrimination and initiation of procurement movement in operant bar press feeding behavior. Of 429 neurons tested, 68 (16%) responded during visual phase. Of these, 30 (7%) responded selectively to the sight of food or non-food associated with a juice reward, but not to the sight of meaningless non-food or food associated with aversive saline. Neuronal activity related to discrimination was readily influenced by extinction, reversal or satiation. The strength of visual responses was correlated with latency of bar press initiation and speed of bar pressing, but was not related directly to bar press movement. These suggest that the LHA is deeply involved in discrimination of reinforcement or non-reinforcement, and might be associated with higher functions to regulate internal states such as physiological need to get food during operant feeding behavior.     

Morphine and dynorphin(1–13) microinjected into the medial preoptic area and nucleus accumbens: effects on sexual behavior in male rats

The effects on sexual behavior of opiate receptor stimulation within A10 and A14 terminal areas were examined in the following experiments. Morphine (0.01–6 nmol) and dynorphin(1–13) (0.01–3 pmol) were microinjected into the medial preoptic area (MPOA). Morphine (10–100 pmol) and dynorphin (10–100 fmol) injected into the MPOA reduced both the latency to ejaculate and the number of intromissions triggering ejaculation. Morphine (6 nmol) produced a failure to resume copulating following the second ejaculation. Morphine (1–10 nmol) injected into the nucleus accumbens (ACC) shortened the latency to the first intromission and lengthened the second postejaculatory interval. Naloxone (3 mg/kg i.p.) reversed the effects of morphine on intromission latency and attenuated the lowering of ejaculatory threshold.     

Neuroanatomical specificity of prolactin-induced hyperphagia in virgin female rats

Intracerebroventricular (i.c.v.) administration of PRL increases food intake in virgin female rats but the brain site(s) at which PRL acts to promote feeding behavior is not known. The present studies investigated the role of the paraventricular nucleus (PVN), ventromedial nucleus (VMH), and medial preoptic nucleus (MPOA) in the hyperphagic actions of PRL. Ad-libitum-fed virgin female rats received twice daily site-specific injections of PRL (800 ng) over a period of 10 days. Only subjects demonstrating regular vaginal cyclicity were included in the study. Food intake, body weight, and vaginal cyclicity were measured daily. Results showed that PRL significantly increased food intake when injected into the PVN. A nonsignificant trend towards a hyperphagic response in the last 5 days of testing was observed in rats receiving intra-VMH injections of PRL, and the MPOA was not responsive to the feeding-stimulating properties of PRL. None of the manipulations affected body weight or vaginal cyclicity as demonstrated by vaginal smears. In sum, the present results reveal that one brain site at which PRL acts to increase food intake is the PVN, but these studies do not rule out the possibility that the effects of PRL on food intake may also involve other brain areas.     

Sexual differentiation and hormonal control of the sexually dimorphic medial preoptic nucleus in the quail

We recently identified a sexually dimorphic nucleus in the preoptic region of the Japanese quail, the medial preoptic nucleus (POM), which is significantly larger in males than in females. In the present study, we investigated the hormonal control of this morphological neuroanatomical difference and the possible relationships between the sexual dimorphism in POM volume and in copulatory behavior. Treatments which are known to affect sexual behavior were thus applied to different groups of birds and the POM volume was then measured. In one experiment, male and female quails were either gonadectomized, gonadectomized and treated with testosterone or left intact. The larger size of the POM in males was confirmed and treatments significantly affected the nucleus size which was decreased by gonadectomy and restored by testosterone treatment in both sexes to a level similar to that seen in intact males. In two other experiments, eggs were injected with estradiol benzoate on day 9 of incubation and the POM volume was measured in adulthood either in intact birds or in gonadectomized birds receiving a replacement therapy with testosterone. Despite the fact that estradiol benzoate treatment completely suppressed copulatory behavior, it did not affect the volume of the POM or slightly increased it. These data thus show that the POM volume is controlled by testosterone levels in adulthood and could thus be an interesting model for the study of the effects of steroids on the brain.     

Ibotenic acid-induced lesions of the medial preoptic area/anterior hypothalamus enhance the display of progesterone-facilitated lordosis in male rats

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. These data are consistent with the hypothesis that cell bodies, rather than axons of passage, originating in the MPOA/AH exert tonic inhibitory control over the display of progesterone-facilitated lordosis in adult male rats.