Effects of pergolide and bromocriptine on male rat sexual behavior

Summary Intact adult male rats were treated with bromocriptine 0–20 mg/kg and pergolide 0–3.2 mg/kg. Two hours after the injection of the respective drug the male rat was presented with a receptive female and various components of the sexual behavior were recorded. Pergolide produced a dose-dependent decrease in the number of intromissions preceding ejaculation and a shortening of the ejaculation latency. The only effect observed after the injection of bromocriptine was an increase in the post-ejaculatory interval at high doses.     

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.     

Sexual stimulation activates c-fos within estrogen-concentrating regions of the female rat forebrain

Regions of the brain that concentrate estrogen and progesterone are thought to regulate female sexual behavior by altering gene expression and neural sensitivity to afferent stimulation. We used immunocytochemistry and in situ hybridization to examine c-fos gene expression within estrogen-concentrating regions of the forebrain following various types of sexual stimulation with or without hormone treatment. Ovariectomized rats received injections of estradiol benzoate 48 h and progesterone 4 h before testing. Control rats that had been ovariectomized at least 5 months before testing did not receive hormone treatment. Rats were then either placed into bilevel testing chambers with sexually vigorous males, received manual stimulation of the flanks, received vaginocervical stimulation with a glass rod, or were left in their home cages. Copulation with intromission and ejaculation in hormone-treated rats, or stimulation of the vaginal cervix in both hormone-treated and control rats, produced a dramatic induction of c-fos mRNA and Fos-like immunoreactivity in estrogen-concentrating regions, such as the lateral septum, medial preoptic area, bed nucleus of the stria terminalis, paraventricular nucleus of the hypothalamus, ventromedial hypothalamus, lateral habenula, and medial amygdala, in addition to regions that do not readily concentrate estrogen, such as the neocortex, thalamus, and striatum. Mechanical stimulation of the flanks produced a smaller induction of Fos in these rats, whereas hormone treatment alone had no effect. These data demonstrate that afferent sensory stimulation, but not estrogen or progesterone, regulates c-fos gene expression within different estrogen-concentrating and non-concentrating regions of the female rat forebrain.     

Comparative behavioral changes between male and female postpubertal rats following neonatal excitotoxic lesions of the ventral hippocampus

Neonatal ventral hippocampal (nVH) lesioned male rat has been used as a model to test the hypothesis that early neurodevelopmental abnormalities lead to behavioral changes putatively linked to schizophrenia. There are significant gender differences in schizophrenia with male and female individuals differing in the age of onset, course and outcome of the disorder. In order to assess whether the behavioral effects of nVH lesions extend to or are different in female rats, we investigated spontaneous locomotion, grooming, social interactions and spatial memory in male and female rats post-pubertally at postnatal day (P) 56 following bilateral ibotenic acid of the ventral hippocampus at P7. The spontaneous locomotor activity in a novel environment of both male and female nVH lesioned rats was significantly enhanced compared to their respective sham-operated controls. In tests of social interactions, the number of encounters was significantly decreased in female lesioned rats, whereas the male nVH lesioned rats showed a significantly reduced duration of active social interactions. Furthermore, Morris water maze test showed a deficit of spatial learning/memory in only male lesioned rats with significant decrease in the latency to find hidden platform. These results suggest that while nVH lesions affect post-pubertal behavior in both sexes of rats, the males appear to be affected to a greater extent than the females underscoring the influence of sex differences in the development of behaviors in the nVH lesioned animals.     

Ibotenic acid lesions of the medial preoptic area disrupt the expression of partner preference in sexually receptive female rats

The present study evaluated the effects of ibotenic acid lesions of the medial preoptic area (mPOA) on the display of partner preference in ovariectomized, estrogen- and progesterone-primed rats. Preference for a sexually vigorous male or an estrous female rat was determined in one of two conditions: unlimited physical access to the stimulus rats (Contact condition) or access that was limited to olfactory, auditory and visual cues (No-contact condition). Lesions of the mPOA reduced the male preference, social preference, and arena crossings, independent of test condition. However, the reduction in male preference following mPOA lesions was most pronounced during tests with unlimited physical access. These results suggest that the mPOA may be involved in integrating somatosensory signals from coital stimulation with the motor responses associated with the appetitive aspects of female sexual behavior.     

Sleep homeostasis in the female rat during the estrous cycle

To investigate whether sleep homeostasis in the female rat is modulated by the estrous cycle, the vigilance states, EEG power spectra and cortical temperature (T_CRT) were assessed on the basis of 4-day continuous recordings. A regulatory response was elicited by 6-h sleep deprivation (SD) during the proestrous (PRO) and the estrous (EST) day and compared to the baseline recordings. The vigilance states varied across the estrous cycle. In the PRO dark period the amount of sleep was reduced. The decrease in rapid-eye-movement (REM) sleep was already evident towards the end of the preceding light period, and an increased fragmentation of sleep was present throughout PRO. Compared to the other days of the estrous cycle, slow-wave activity (SWA; EEG power density 0.75–4.75 Hz) in nonREM (NREM) sleep was lower in PRO at the end of the light period and in the beginning of the dark period. High-frequency activity (HFA; EEG power density 10.25–25.0 Hz) was increased in the dark period of PRO. The SD performed during the first 6 h of the light period of PRO and EST enhanced SWA in NREM sleep and reduced sleep fragmentation during the subsequent 6 h. The extent and time course of the response to SD did not differ between the two phases of the estrous cycle. It is concluded that despite the marked baseline variations of the vigilance states and the EEG, homeostatic regulation is little affected by the estrous cycle.     

Quantitative assessment of female sexual motivation in the rat: Hormonal control of motivation

While a good deal of information has been garnered in the last few decades regarding the neural and hormonal control of female sexual behavior, literature elucidating these mechanisms with respect to female sexual motivation has been scarce. We believe that one reason for this is the lack of a standardized paradigm that will quantify female sexual motivation while allowing for sexual interaction to occur. Here we describe a two-chambered apparatus that utilizes operant responding (nose poking) to quantify female sexual motivation. During the test, the female exhibits nose pokes to gain access to a sexually active male, with whom she is allowed to mate. Therefore, this apparatus allows for examination of sexual behavior as well as quantification of sexual motivation by assessing the number of nose pokes the female will exhibit within a fixed interval to gain access to the male.We report that hormone priming significantly increases sexual motivation in the female as indicated by the number of nose pokes she will exhibit to gain access to the male. Additionally, hormone primed females enter the male compartment after a shorter period and spend more time in direct contact with the male compared to when they are not hormone primed. In contrast, when females are not hormone primed they spend more time in view, but out of reach, of the male.This paradigm will help to advance the study of female sexual motivation, providing a method for quantifiable assessment of female sexual motivation while allowing for sexual activity to occur.     

Cholinergic limbic projections and behavioral role of basal forebrain nuclei in the rat

The purposes of the present study were to identify cholinergic non-neocortical projections of the basal forebrain and to determine the role of this region in the regulation of estrogen-dependent reproductive behaviors in the rat. Bilateral electrolytic lesions were placed in an area encompassing the horizontal limb of the diagonal band, as well as portions of the substantia innominata and magnocellular preoptic nucleus, and choline acetyltransferase (CAT) activity was assayed in microdissected brain areas seven days after lesion. Compared to sham surgery, lesions of this region significantly reduced CAT activity in the basal amygdala (34%), dorsal hippocampus (14%), cingulate cortex (25%), piriform cortex (36%), and entorhinal cortex (34%). Other limbic and midbrain structures do not appear to receive significant cholinergic innervation from this locus since no reductions in CAT were detected after bilateral lesions. These included the anterior hypothalamus, ventromedial hypothalamus, mammillary nucleus, habenula, subiculum, ventral hippocampus, insular cortex, central gray, and interpeduncular nucleus. Behaviorally, female rats with bilateral lesions of the basal forebrain displayed an unusually high incidence of rejection behavior in response to attempted mounts by stimulus male rats in sexual behavior tests. There was no effect of basal forebrain lesions on the incidence of lordosis exhibited by these females. The dissociation of rejection and lordosis suggests that distinct neural pathways mediate the occurrence of these reproductive behaviors and that rejection behavior may be regulated by basal forebrain pathways.     

Suppression of mating behaviour in the male rat by intracerebroventricular infusions of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Acute microinfusions of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the third cerebral ventricle (III V) of sexually experienced male rats produced a dose-related suppression of masculine sexual behaviour. This inhibition of male sexual performance could be reversed by simultaneous infusions of small doses of pargyline. Three analogues of MPTP, namely, 4-phenyl-1,2,3,6-tetrahydropyrididine, 4-cyano-4-phenylpiperidine and 4-hydroxy-4-phenylpiperidine had no significant effects on any of the parameters of male sexual behaviour. These findings suggest that MPTP may have potent effects on the mechanisms regulating male sexual behaviour in the rat by acting on sites around the third ventricle (arcuate and periventricular hypothalamic nuclei) where there are high MPTP receptor densities and thus provide further evidence for MPTP in neuroendocrine regulation. These responses depend upon the unique structural properties of the MPTP molecule.     

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.     

Brain monoaminergic control of male reproductive behavior. III. Norepinephrine and the post-ejaculatory refractory period

The present study was performed to examine the role of brain norepinephrine in the control of copulation and the post-ejaculatory refractory period in the male rat. Disruption of central noradrenergic systems was achieved by (1) selective electrolytic lesion of noradrenergic cell bodies in the locus coeruleus or (2) administration of specific inhibitors of norepinephrine synthesis, sodium diethyldithiocarbamate (DDC) or 1-phenyl-3-(2-thiazolyl)-2 thiourea (U-14, 624). Electrolytic lesions of the locus coeruleus produced a significant increase in the duration of the post-ejaculatory refractory period and its concomitant 22-kHz ultrasonic vocalization. Administration of norepinephrine synthesis inhibitors significantly increased both mount and intromission latencies and caused a dramatic increase in the length of the post-ejaculatory refractory period. These findings support the hypothesis that norepinephrine-containing neural pathways are involved in the control of sexual arousal and suggest that a functional noradrenergic system is essential to the integrity of normal masculine copulatory behavior.     

Hypothalamic testosterone increase in the male rat at birth

In the male rat, a dramatic increase in serum testosterone occurs during the first 2 h of postnatal life. Since the hypothalamus is known to be an important site for sexual differentiation of the brain, this early testosterone surge was a good model to use to study the transfer of serum testosterone to the hypothalamus and cerebral cortex. Endogenous testosterone was measured by radioimmunoassay in the hypothalamus and the cerebral cortex of the foetus and newborn rats during the first 6 h following birth. In the male, hypothalamic testosterone increased between 0 h in utero and 2 h; in the males gonadectomized at 0 h in utero and killed at the age of 2 h, the testosterone surge was abolished, clearly indicating the testicular origin of this hormone in the neonate. The small testosterone increase in the cerebral cortex compared with that in the hypothalamus reflects a preferential uptake of this hormone by the hypothalamus of the newborn. In the female, hypothalamic testosterone slightly decreased between 0 h in utero and 6 h. These results are in agreement with the view that hypothalamic modifications form the basis for some behavioral and physiological changes attributed to the effect of perinatal hormonal stimulation.     

Acute luteinizing hormone and prolactin responses to paced mating stimulation in the estrous female rat

The present experiments sought to characterize the particular stimuli received during mating in the female rat which induce acute increases in luteinizing hormone (LH) and prolactin (PRL) following copulation. Comparisons were made between cycling females mated on the evening of proestrus in partitioned chambers in which spontaneous patterns of approach/withdrawal toward the male served to pace copulatory stimulation (paced), in non-partitioned chambers in which female regulation of intervals between copulatory mounts was prevented (non-paced), or under conditions in which they received mounts-without-intromission (mounts-only). Frequent blood samples were withdrawn via surgically implanted intra-atrial catheters. In experiment 1, blood samples for LH determinations were taken at 15-min intervals for 1 h prior to and for 2 h after mating on the evening of proestrus. In experiment 2, samples for PRL determinations were taken at 10-min intervals for 30 min prior to and for 90 min after mating on proestrus and at 0300, 0400 and 0500 h on the day of estrus (reported times corrected for reversed light cycle). LH levels were significantly higher in paced animals 15 min after initiation of mating than in non-paced and mounts-only females; no differences in LH were seen between females who subsequently became or did not become pregnant/pseudopregnant (P/PSP). PRL values were not different between groups receiving the different mating treatments at any time; however, P/PSP animals showed significantly higher levels of PRL between 20 to 60 min after mating than did non-P/PSP females. No differences in PRL were seen between mating treatments or pseudopregnancy condition at 0300 to 0500 h on estrus. Paced females in both experiments received intromissions at a significantly slower rate than did non-paced females. There was a significant positive correlation (r = 0.619, P<0.001) between LH concentration at 15 min and the inter-intromission interval (in seconds) in paced and non-paced groups of females. These data suggest that an LH response to mating is dependent upon the particular characteristics of mating stimulation received. In addition, they demonstrate that PRL increases acutely after mating stimulation in animals destined to become P/PSP but does not increase in response to those characteristics of mating stimulation which induced increases in LH.     

Effects of hypothalamic and preoptic lesions on reproductive behavior in male rats

Adult male rats, which were selected on the basis of showing complete patterns of male copulatory behavior on two prior tests, were castrated six weeks prior to brain surgery. Animals were divided into three groups and given small bilateral lesions in the dorsomedial preoptic area (POA), ventromedial hypothalamus (VMH), or sham operations. Starting 10 days postsurgery, all animals were injected with estrogen alone and estrogen plus progesterone, and tested twice for lordosis behavior. Ten days following the female behavior tests, animals were injected daily with testosterone propionate for 13 days and tested for masculine sexual behavior on injection days 5, 9 and 13. Low levels of lordotic behavior were observed for POA and VMH animals on both tests for female sex behavior and were comparable to sham operated animals. However, in terms of all dependent measures of male copulatory behavior, animals with VMH lesions showed significantly higher levels of male sex behavior with shorter latencies than sham animals across all three behavior tests. In contrast, POA lesioned rats showed little or no male sex behavior on any test and were significantly inferior to sham operated animals. Thus, the POA and VMH appear to exert excitatory and inhibitory control, respectively, over male copulatory behavior in male rats.     

Perinatal exposure to polychlorinated biphenyls differentially affects cerebellar development and motor functions in male and female rat neonates

Perinatal exposure to polychlorinated biphenyls (PCBs) interacts with genetics and impacts the course of the central nervous system (CNS) development in both humans and animals. To test the hypothesis that the neurobehavioral impairments, and specifically motor dysfunctions following perinatal PCB exposure in rats are associated with changes in a specific brain region, the cerebellum, we compared neurodevelopment, motor behavior, cerebellar structure, and protein expression in rat neonates exposed to the PCB mixture Aroclor 1254 (A1254, 10.0 mg/kg/day) from gestational day 11 until postnatal day (P) 21 with that of controls. Body mass of PCB-exposed pups was not affected at birth, but was significantly lower than that of controls between birth and weaning; by P21 the difference was greater in females than in males. A1254 exposure delayed ear unfolding and impaired performance on the following behavioral tests: (1) righting response on P3-P6; (2) negative geotaxis on P5-P7; (3) startle response on P10-P12; and (4) a rotorod on P12, with PCB-male pups more severely affected than female. Changes in the behavior of PCB pups were associated with changes in cerebellar structure and protein expression. Cerebellar mass was more reduced in PCB-male than PCB-female pups. Analysis of selected cerebellar proteins revealed an increase in GFAP expression, greater in male than in female, and a decrease in L1 expression in both sexes. These results suggest that PCB exposure affects behavior and cerebellar development differently in male and female rat neonates, with greater effects in males. Further studies of neonatal PCB exposure will establish whether the environmental pollutants can contribute to the sex-related preponderance of certain neuropsychiatric disorders.     

Lesions of the preoptic area facilitate lordosis behavior in male and female guinea pigs

Male and female guinea pigs received radiofrequency lesions in the medial preoptic area (MPOA). Animals were gonadectomized, treated with estrogen and progesterone, and tested for the occurrence of the lordosis response to manual stimulation. Females with MPOA lesions exhibited enhanced lordosis behavior, shorter latencies to heat, longer duration of heat and longer maximum lordosis duration than sham control females. In males with MPOA lesions, the lordosis response could be elicited by manual stimulation, in contrast to no response in the sham control males. Furthermore, MPOA-lesioned males were insensitive to the inhibitory effects of progesterone on lordosis behavior, while MPOA-lesioned females were as sensitive as sham controls to the inhibitory effects of progesterone. The results suggest that a neural mechanism resides within the MPOA which inhibits the occurrence of lordosis behavior in both male and female guinea pigs and which is not involved in a sexual dimorphism in responsiveness to progesterone.     

Role of opioidergic and monoaminergic neurotransmission in the GnRH release mechanism of EBP-primed OVX rats

We examined the effect of intracerebroventricular (i.c.v.) administration of μ-opioid agonist, morphine, and its antagonist naloxone followed by morphine on the activities of monoamine-metabolizing enzymes, namely tyrosine hydroxylase (TH) and monoamine oxidase (MAO) along with adenosinetriphosphatase (Na⁺, K⁺ -ATPase), the enzyme responsible for the maintenance of ionic gradients across the membrane, in seven discrete regions of brain from estrogen- and progesterone-primed ovariectomized rats. TH activity decreased after morphine treatment in some areas such as the median eminence-arcuate region (ME-ARC), the amygdala, and the thalamus, showing statistically significant change. MAO activity increased in all the areas studied, but more appreciable change was observed in medial preoptic area (mPOA), the ME-ARC region, and the cortex. Pronounced increase in Na⁺, K⁺ -ATPase enzyme activity was observed after the drug treatment. Naloxone given prior to morphine injection resulted in recovery of the enzyme activities in most of the areas studied. Our study may provide insights into the precise opioidergic modulation of gonadotropin releasing hormone (GnRH) release mechanisms through the involvement of monoaminergic system, elucidating the basis of various neuronal dysfunctions and their management in opioid addicts.     

Sexual behavior enhances central dopamine transmission in the male rat

Central dopamine transmission was examined in the nucleus accumbens and striatum of sexually experienced male rats during mating behaviour using in vivo brain microdialysis. Dopamine release increased significantly in the nucleus accumbens when males were placed in a novel mating chamber and when a receptive female was introduced behind a screen partitioning this chamber. Subsequently, during copulation dopamine transmission increased sharply, this being followed by a gradual decrease after the female was removed. In contrast, striatal dopamine transmission increased significantly only during copulation. These data provide a neurochemical basis for the well-known interactions between dopaminergic drugs and male sexual behaviour and demonstrate the feasibility of using brain microdialysis to elucidate the neurochemical correlates of motivated behaviour.     

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.     

Brain monoaminergic control of male reproductive behavior. I. Serotonin and the post-ejaculatory refractory period

The present experiment was performed to examine the role of serotonergic mechanisms in the control of copulation and the post-ejaculatory refractory period in the male rat. Disruption of central serotonergic systems in two separate groups of animals was achieved by: (1) selective electrolytic lesions of the midbrain raphe nuclei, or (2) localized intraventricular or intracerebral injection of a specific serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT). A third group of animals was tested for sexual behavior following intraperitoneal injection of p-chlorophenylalanine (PCPA), an inhibitor of serotonin synthesis. Both electrolytic and neurochemical lesions localized in the dorsal raphe nucleus produced a highly significant shortening of the ejaculatory latency, and the post-ejaculatory refractory period. Disruption of serotonergic mechanisms following intraventricular injection of 5,7-DHT or systemic administration of PCPA also caused a significant reduction in the length of the refractory period. These results support the hypothesis that central serotonergic systems are normally inhibitory to certain facets of male copulatory behavior and suggest the existence of a serotonergic control system which normally exerts an inhibitory influence over the resumption of mating following ejaculation.