The yin/yang of inflammatory status: Blood-brain barrier regulation during sleep.

Sleep loss induces a low-grade inflammatory status characterized by a subtle but sustained increase of pro-inflammatory mediators, which are key regulators of blood-brain barrier function. To investigate the influence of inflammatory status on blood-brain barrier dysfunction induced by sleep restriction we performed an experiment using two strains of mice with different immunological backgrounds, C57BL/6 mice that have a predominant pro-inflammatory response and BALB/c mice that have a predominant anti-inflammatory response. Mice were sleep-restricted during 10 days using the flowerpot technique during 20 h per day with 4 h of daily sleep opportunity. The systemic inflammatory status, blood-brain barrier permeability, and the hippocampal expression of neuroinflammatory markers were characterized at the 10th day. Serum levels of TNF and IFN-γ increased in sleep-restricted C57BL/6 but not in BALB/c mice; no changes in other cytokines were found. Sleep restriction increased blood-brain barrier permeability in C57BL/6 strain but not in BALB/c. The hippocampus of sleep-restricted C57BL/6 mice exhibited an increase in the expression of the neuroinflammatory markers Iba-1, A2A adenosine receptor, and MMP-9; meanwhile in sleep-restricted BALB/c mice the expression of this markers was lesser than the control group. These data suggest that cytokines may be playing a key role in modulating blood-brain barrier function during sleep restriction, and probably the effects are related to Iba-1, MMP-9 and A2A adenosine receptor overexpression.

Chronic sleep restriction disrupts interendothelial junctions in the hippocampus and increases blood-brain barrier permeability.

Chronic sleep loss in the rat increases blood-brain barrier permeability to Evans blue and FITC-dextrans in almost the whole brain and sleep recovery during short periods restores normal blood-brain barrier permeability. Sleep loss increases vesicle density in hippocampal endothelial cells and decreases tight junction protein expression. However, at the ultrastructural level the effect of chronic sleep loss on interendothelial junctions is unknown. In this study we characterised the ultrastructure of interendothelial junctions in the hippocampus, the expression of tight junction proteins, and quantified blood-brain barrier permeability to fluorescein-sodium after chronic sleep restriction. Male Wistar rats were sleep restricted using the modified multiple platform method during 10 days, with a daily schedule of 20-h sleep deprivation plus 4-h sleep recovery at their home-cages. At the 10th day hippocampal samples were obtained immediately at the end of the 20-h sleep deprivation period, and after 40 and 120 min of sleep recovery. Samples were processed for transmission electron microscopy and western blot. Chronic sleep restriction increased blood-brain barrier permeability to fluorescein-sodium, and decreased interendothelial junction complexity by increasing the frequency of less mature end-to-end and simply overlap junctions, even after sleep recovery, as compared to intact controls. Chronic sleep loss also induced the formation of clefts between narrow zones of adjacent endothelial cell membranes in the hippocampus. The expression of claudin-5 and actin decreased after chronic sleep loss as compared to intact animals. Therefore, it seems that chronic sleep loss disrupts interendothelial junctions that leads to blood-brain barrier hyperpermeability in the hippocampus.

Blood-Brain Barrier Disruption Induced by Chronic Sleep Loss: Low-Grade Inflammation May Be the Link.

Sleep is a vital phenomenon related to immunomodulation at the central and peripheral level. Sleep deficient in duration and/or quality is a common problem in the modern society and is considered a risk factor to develop neurodegenerative diseases. Sleep loss in rodents induces blood-brain barrier disruption and the underlying mechanism is still unknown. Several reports indicate that sleep loss induces a systemic low-grade inflammation characterized by the release of several molecules, such as cytokines, chemokines, and acute-phase proteins; all of them may promote changes in cellular components of the blood-brain barrier, particularly on brain endothelial cells. In the present review we discuss the role of inflammatory mediators that increase during sleep loss and their association with general disturbances in peripheral endothelium and epithelium and how those inflammatory mediators may alter the blood-brain barrier. Finally, this manuscript proposes a hypothetical mechanism by which sleep loss may induce blood-brain barrier disruption, emphasizing the regulatory effect of inflammatory molecules on tight junction proteins.

Effect of low-frequency repetitive transcranial magnetic stimulation on sleep pattern and quality of life in patients with focal epilepsy.

OBJECTIVE: In this study we analyzed the effects of transcranial magnetic stimulation (TMS) on sleep and on the self-perceived quality of life in epileptic patients. METHODS: A total of 24 male patients diagnosed with focal epilepsy were included in the study. Pharmacological treatment with levetiracetam was standardized at 2 g daily. Before TMS onset, all-night polysomnographic recording (PSG) was performed, and the Quality of Life in Epilepsy Inventory (QOLIE-31) was administered. Thereafter, patients underwent low-frequency repetitive TMS (1000 pulses/1 Hz) daily for 10 days. After the end of the treatment, a second polysomnographic study was performed, and the QOLIE-31 questionnaire was administered again. RESULTS: TMS induced a significant increase in sleep efficiency and in total sleep time, along with a decrease in sleep latency and the number of awakenings. In addition, the number of interictal discharges during sleep decreased significantly. Concerning the QOLIE-31 scale values, the patients showed great improvement in the self-perceived quality of life. CONCLUSION: The present results indicate that TMS may mediate therapeutic effects in the treatment of patients with focal epilepsy, and that TMS treatment is accompanied by improvement of sleep patterns as well as improvement in self-perceived quality of life. However, a study that includes a control group undergoing sham stimulation is needed to confirm these findings.

Steroid hormones and sleep regulation.

In the search of the sleep substance, many studies have been addressed for different hormones, responsible for sleep-wake cycle regulation. In this article we mentioned the participation of steroid hormones, besides its role regulating sexual behavior, they influence importantly in the sleep process. One of the clearest relationships are that estrogen and progesterone have, that causing changes in sleep patterns associated with the hormonal cycles of women throughout life, from puberty to menopause and specific periods such as pregnancy and the menstrual cycle, including being responsible for some sleep disorders such as hypersomnia and insomnia. Another studied hormone is cortisol, a hormone released in stressful situations, when an individual must react to an extraordinary demand that threatens their survival, but also known as the hormone of awakening because the release peak occurs in the morning, although this may be altered in some sleep disorders like insomnia and mood disorders. Furthermore neurosteroids such as pregnanolone, allopregnanolone and pregnenolone are involved in the generation of slow wave sleep, the effect has been demonstrated in experimental animal studies. Thus we see that the sleep and the endocrine system saved a bidirectional relationship in which depends on each other to regulate different physiological processes including sleep.

Polysomnographic features in infants with early diagnosis of congenital hypothyroidism.

Thyroid hormones play a major role in the maturation process of the brain. Currently, congenital hypothyroidism is detected by mass screening. The impact of this early hormonal deficiency on the organization of the sleep pattern is not known. In this study, the polysomnographic features in children diagnosed with congenital hypothyroidism were analyzed. Children were detected by mass population screening and the hormonal replacement therapy starts immediately. Children's age ranged between 1.5 and 18 months of age. The duration of hormonal treatment before sleep recordings varied between 8 days and 17 months. Children were polysomnographically recorded in the morning, for at least 2h, obtaining more than one sleep cycle. Results showed a high prevalence of females (5/1) in the group studied. A high proportion of infants (43%) displayed central apnea in different degrees (mild, moderate and severe) as well as hypopnea (83%), mainly in subjects around 4 and 8 months of age. The proportion of infants displaying central apnea decreases as age increases. In addition, indeterminate (light) sleep increase and quiet (slow wave) sleep decrease significantly regardless of age and treatment. The percentage of REM sleep correlated positively with the age of the child at the beginning of the treatment, and negatively with their age at the time of the study. These data indicate that congenital hypothyroidism facilitates the presence of central sleep apnea. The decrease of these respiratory alterations correlates with the increase of the hormonal replacement therapy. It seems that sleep respiratory alterations in congenital hypothyroidism are linked to brain maturation processes in which thyroid hormones play a major role.

The H1 histamine receptor blocker, chlorpheniramine, completely prevents the increase in REM sleep induced by immobilization stress in rats.

Chlorpheniramine is a selective antagonist of the H1 histaminergic receptor subtype and its effects in humans include somnolence. Chlorpheniramine affects sleep in rats, mainly by decreasing REM sleep. On the other hand, stress by immobilization induces an important increase in the percentage of REM sleep. In this study we analyzed the effects of blocking histaminergic receptors on REM sleep induced by immobilization stress. Adult male Wistar rats were chronically implanted for sleep recording. Immobilization stress was induced by placing the rat in a small cylinder for 2 h. Experimental conditions were: A. Control; B. Stress; C. Stress plus vehicle and D. Stress plus chlorpheniramine. Independent experiments were done both in the dark, as well as the light period. Results showed that the increase in REM sleep observed after immobilization stress was completely abolished by chlorpheniramine, both in the dark and in the light phase. Furthermore, the decrease in REM sleep was significant even when compared to the non-stressed control rats. REM sleep latency was also significantly longer during both light phases. The present results suggest that REM sleep is quite sensitive to histaminergic blockage. It is possible that chlorpheniramine is also blocking the cholinergic mechanisms generating REM sleep.

Sexual behavior of female rats in a multiple-partner preference test.

In this study, sexually experienced female rats were tested in a multiple-partner preference test (MPPT) in which they were allowed to pace their sexual contacts with four sexually active males. Four cylinders, with a small hole through which only the female could move freely from one cylinder to another, were assembled forming in the center an empty compartment. An intact female was placed in the central compartment and a sexually active male in each cylinder. Female sexual behavior was analyzed throughout the estrus cycle in four consecutive days. Each daily test lasted 15 min. The percentage of exits after intromission or ejaculation was significantly higher than the percentage of exits after each mount. The female spent significantly longer time with one of the males. We designated this male as the preferred male (PM). Although in each of the 4 days studied, females spent significantly longer time with the PM, however, the male selected was not the same throughout the estrus cycle. The number of entries into the compartment of the PM was significantly higher and increased around proestrus. Compared to previous studies, pacing behavior was notably lower in the conditions of the MPPT. No significant differences were observed during the estrous cycle concerning the other parameters recorded. The present results suggest that the MPPT could be a good model to study partner preference in the female rat.

Antidepressant-like effects of the acute and chronic administration of nicotine in the rat forced swimming test and its interaction with fluoxetine [correction of flouxetine].

An antidepressant action of nicotine (NIC) has recently been suggested. Flouxetine, a selective serotonin reuptake inhibitor, is currently the most widely used antidepressant. In the present study, we analyzed the effects of the administration of NIC, fluoxetine (FLX), and the combination of both drugs given acutely, subchronically, and chronically as well as 7 days after chronic administration of these drugs on the forced swim test. Results showed that NIC induced a significant reduction of the time in immobility during the forced swim test (antidepressant effect), with a concomitant increase in swimming activity (serotonergic activation), after acute administration. These effects remain the same after subchronic and chronic administration. FLX failed to induce any effect after acute administration but did induce a significant decrease of immobility and an increase of swimming after subchronic administration. The effect of the chronic administration was significantly larger compared to subchronic administration. The combination of both drugs induced a larger effect than that observed after a single administration but only after subchronic treatment. No effect was observed after the end of the 7-day treatments. Data suggest that NIC has an antidepressant action that is expressed faster than FLX but remains the same later. Thus, cholinergic-serotonergic interactions could play an important role in the treatment of depression.

Stress-induced REM sleep increase is antagonized by naltrexone in rats.

RATIONALE: The expression of sleep is influenced by situations that take place during the preceding waking period, giving rise to different patterns of sleep architecture. Immobilization stress (IMB) induces an increase of both rapid eye movement (REM) and slow wave sleep (SWS). It has been suggested that these changes are mediated in part by noradrenaline and by the corticotrophin releasing factor. OBJECTIVE: To determine the participation of mu receptors in the stress-induced increase of REM sleep using naltrexone (NTX). METHODS: Twelve adult male rats were implanted for sleep recordings. Subjects were recorded under control conditions as well as after: a) IMB stress (1 h); b) injection of NTX (1.5 mg/kg); c) NTX plus IMB. To assess corticosterone levels, additional groups ( n=5) were decapitated at 0, 1, 3 and 6 h after vehicle injection and after immobilization. Four groups were decapitated at 0, 1, 3, and 6 h after NTX plus IMB. Corticosterone plasma levels were determined by HPLC. RESULTS: IMB induces an increase in REM and SWS, and a decrease in wakefulness. Administration of NTX before IMB suppresses the effects of stress on sleep. NTX administration is innocuous in non-stressed animals. However, NTX administration does not prevent the rise of corticosterone normally observed after IMB stress. CONCLUSION: These data suggest that NTX prevents the effects of IMB stress on sleep by acting outside of the hypothalamic-pituitary-adrenal axis that partially mediates the stress response.

Changes in masculine sexual behavior, corticosterone and testosterone in response to acute and chronic stress in male rats.

Chronic exposure to stressors increases HPA axis activity and concomitantly reduces HPG axis activity. This antagonistic relationship between both these axes has been proposed to underlie the inhibition of reproductive function due to stress. Sexual behavior in males may be the most vulnerable aspect of male reproduction to acute and chronic stress and it has been suggested that alterations in sexual behavior during stress are due to the antagonistic relationship between testosterone and corticosteroids. However, only in a few studies has a correlation between the levels of testosterone and corticosterone, and sexual behavior been made. In this study, we evaluated the effects of different stressors, applied both acute and chronically, on masculine sexual behavior and whether or not these effects on sexual behavior are accompanied by changes in plasma levels of corticosterone and testosterone. Additionally, we evaluated the effect of testosterone treatment on the effects of stress on sexual behavior. Sexually experienced male rats were exposed to one of the following stressors: immobilization (IMB), electric foot shocks (EFS) or immersion in cold water (ICW). Sexual behavior and plasma levels of testosterone and corticosterone were assessed on days 1, 5, 10, 15, and 20 of stress. In a second experiment, males were castrated, treated with 3 different doses of testosterone propionate (TP) and exposed to ICW for 20 consecutive days. Sexual behavior was assessed on days 1, 5, 10, 15, and 20 and steroids were evaluated on day 20. Parameters of masculine sexual behavior were modified depending on the characteristics of each stressor. Mount, intromission and ejaculation latencies increased significantly, the number of mounts increased, and ejaculations decreased significantly in males exposed to EFS and to ICW but not in males exposed to IMB. Associated with these effects, testosterone decreased in the EFS and ICW groups on days 1, 15, and 20. However, corticosterone increased only in males exposed to ICW. In castrated males, TP treatment failed to block the effects of stress by ICW on sexual behavior and corticosterone. These results indicate that the effects of stress on sexual behavior depend on the characteristics of each stressor, and these effects, as well as the decrease in testosterone are not necessarily associated with the increase in corticosterone. The fact that testosterone treatment did not prevent the effects of stress on sexual behavior suggests that other mediators could be involved in the alterations of sexual behavior caused by stress.

Corticosterone and testosterone levels after chronic stress in an animal model of depression.

Neonatal administration of clomipramine (CMI) in rats induces behavioral changes during adulthood, such as impairments of pleasure-seeking behaviors. However, the endocrine changes induced by this treatment are controversial. In the present study, we analyzed the levels of corticosterone and testosterone in rats neonatally treated with CMI in response to chronic stress by repeated immersion in cold water. Results obtained in the forced swim test corroborated the effect of neonatal CMI administration, showing a significant increase in immobility time. The testosterone response to stress was similar in both control and CMI-treated rats. Concerning corticosterone, there was a significantly lower response to stress in CMI-treated rats. The data suggest that CMI induces permanent changes in the reactivity of the hypothalamic-pituitary-adrenal axis, without affecting the hypothalamic-pituitary-gonadal axis.

Plasma levels of corticosterone and testosterone after sexual activity in male rats treated neonatally with clomipramine.

Neonatal treatment with clomipramine (CMI) in rats, induces alterations of pleasure-seeking behaviors during adulthood. Alterations of hormonal responses to stressful situations have also been reported. In this study, the levels of corticosterone and testosterone in response to sexual activity were assessed in rats treated neonatally with CMI. Male pups received subcutaneous injections of CMI (15 mg/kg, 0.1 ml), twice a day (09.00 hours and 18.00 hours) from 8 to 21 days of age. A control group received saline in the same number of injections. Four months after CMI treatment, subjects (Ss) were submitted to the forced swim test to verify the effect of CMI. Thereafter, they were tested to assess their spontaneous sexual activity. Plasma levels of corticosterone and testosterone were assessed under different conditions. Results of sexual behavior and the forced swim test corroborate the depressive-like effect of CMI. The sole presence of an estrogenized stimulus female caused an increase in plasma levels of testosterone in both control and CMI-treated Ss. The same was true for corticosterone; however, this increase was significantly lower in the CMI-treated group. There is a discrepancy between the normal hypothalamus-pituitary-gonadal (HPG) response and the decreased sexual behavior. The data suggest that CMI induces permanent changes in the reactivity of the hypothalamic-pituitary-adrenal axis.

Masculine sexual activity affects slow wave sleep in Golden hamsters.

The sleep pattern is modified by events occurring during wakefulness. In rats, it has been shown that male sexual behavior has a direct influence on sleeping patterns, increasing slow wave sleep (SWS) duration. On the other hand, the sexual behavior pattern of the male Golden hamster differs from the copulatory pattern of male rats. Male hamsters copulate faster and they do not display the motor inhibition observed in rats after each ejaculation. Moreover, close to exhaustion, hamsters display a behavioral pattern known as Long Intromission, which has been linked to an sexual inhibitory process. The present study was performed to determine the effects of male sexual activity on the sleep pattern in hamsters. Subjects were allowed to copulate for 30 and 60 min. In addition, the effect of locomotor activity was also assessed. The results show that male sexual behavior induced a significant increase of SWS II, with a reduction of wakefulness. No effect was observed on REM sleep. Locomotor activity produced only a slight effect on sleep. The results are discussed in terms of the similarities between the effects observed after sexual behavior on sleep in rats and hamsters, despite the substantial differences in the behavioral pattern.

Body weight gain and diurnal differences of corticosterone changes in response to acute and chronic stress in rats.

Plasmatic levels of corticosterone display a circadian rhythm, with the higher values occurring during the dark phase in nocturnally feeding animals. Stressful situations induce a rise of corticosterone levels and this endocrine response to stress also presents circadian variations. The higher increase of corticosterone in response to stress occurs when the hormone is in its lower circadian level, and the minimum responses occurring at the peak. Since it has been shown that plasma hormones respond differently to different stressors, in the present study, we compared the acute and chronic effects of four different stressors: electric foot shocks (3 mA, 1/s, 5 min), immobilization during two hours or six hours, and immersion in cold water (15 degrees C) for 15 min. Stressors were applied, both acutely and chronically (during 4, 12 and 20 days) at the onset of the light phase as well as at the onset of the dark phase of the light/dark cycle. Body weight was assessed every day, and at the end of the manipulations plasmatic corticosterone levels were determined from the trunk blood. Adrenal and testicular weights were also assessed. Acute exposure to stressors increased plasmatic corticosterone levels significantly when the stressors were applied at the beginning of the light phase of the cycle. In the dark phase, only two hours of immobilization and immersion in cold water caused an increase in plasmatic corticosterone. With repeated exposure, electric foot shocks failed to induce significant changes in corticosterone levels in any phase of the light-dark cycle. Immobilization stress induced a significant rise in corticosterone levels only when the stressor was applied during the light phase. Immersion in cold water elicited a clear increase in plasmatic corticosterone levels in all the periods tested, regardless of the time of the cycle in which the stressor was applied. We did not observe a loss in body weight, but rather a smaller weight gain in stressed rats. Body weight gain was minimum in rats exposed to immersion and 6 hours of immobilization. Adrenal hypertrophy was observed in rats exposed to these same stressors. We conclude that: 1) the activation of the hypothalamus-pituitary-adrenal axis by stress depends mainly on the characteristics of the stressor; 2) the response of this axis to stress also depends on the time of day in which the stressor is applied.

Monoaminergic and cholinergic stimulation of masculine sexual behavior in neonatally demasculinized male rats.

Sexual behavior during adulthood largely depends upon hormonal events that take place around birth. Administration of the antiestrogen Tamoxifen (Tx) to males immediately after birth induces a marked decrease of masculine sexual behavior during adulthood. On the other hand, it is well known that masculine sexual behavior can be stimulated by the administration of drugs acting specifically on the monoaminergic or the cholinergic systems. This study was performed to analyze if masculine sexual behavior can be pharmacologically stimulated in adult male rats neonatally demasculinized by the administration of Tx. Neonatal administration of Tx induced clear impairments of masculine sexual behavior during adulthood. Administration of oxotremorine (OXO), 8-OH-DPAT (8-hydroxy-2(di-n-propylaminotetraline)), yohimbine (YH), and apomorphine (APO), drugs that normally elicit a stimulation of masculine sexual behavior were unable to fully restore it in demasculinized males. Only slight improvements of some behavioral parameters were observed with 8-OH-DPAT and YH. OXO seems to induce a worsening of sexual behavior impairments. Results obtained with APO were not significantly different from saline controls. Data suggest that neonatal treatment with Tx induces permanent impairments of the neural circuitry regulating masculine sexual behavior not only limited to morphological changes but also functional alterations of the neurotransmitter systems.

Copulatory activity increases slow-wave sleep in the male rat.

It is believed that sexual activity increases the need to sleep in many species. However, the relationship between copulatory activity and sleep has been poorly studied. Several studies have observed variations in the sleep of female rats and women as a function of their reproductive state. These effects have been correlated with the effects of female steroid hormones, but not with sexual activity. The aim of the present study was to evaluate the sleep-wake pattern of male rats immediately after different conditions of copulatory activity. Sexually experienced male rats were chronically implanted with a standard set of electrodes for sleep recording. After a control sleep recording of 8 h, the males were randomly assigned to one of the following experimental conditions: 30 min in the presence of an ovariectomized (OVX) rat; 30 min in the presence of an intact non-receptive female (NRF); with a receptive female until reaching one ejaculation (1E); and with a receptive female until reaching three ejaculations (3E). In addition, after 10 days, males were randomly exposed to one of the following copulatory conditions during 4 h: to remain in the presence of an OVX rat; to remain in the presence of an NRF female, and with receptive females until reaching sexual satiety (SS). Male sexual behavior was assessed just after the onset of the dark period, and sleep recordings were obtained during 8 h immediately after experimental testing. Both the three ejaculations group (3E) in the first experiment and the sexual satiety group (SS) in the second experiment showed enhanced percentages of time spent in slow wave sleep (SWS) II and a shorter latency to the first SWS II episode than in the control group or under basal conditions. In addition, neither the presence of a non-receptive female or an OVX female, nor sexual behavior until reaching one ejaculation induced any effect on the sleep stages. These findings suggest that the increase in SWS II induced by both 3E and SS may be governed by some specific mechanism that is essentially independent of physical exercise or stress. Copulatory activity might be the source of neurohormonal processes that induce sleep and may involve the participation of gamma-aminobutyric acid, serotonin or other endogenous regulators of sleep and wakefulness. Nevertheless, the precise mechanism by which the sexual behavior increases SWS is still to be determined.

Masculine sexual behavior features in the Flinders sensitive and resistant line rats.

The Flinders sensitive (FSL) and resistant (FRL) lines of rats have been selectively bred for their differences in cholinergic sensitivity. The FSL rats display hypersensitive responses to agonists of muscarinic receptors. In addition, the FSL rats display behavioral alterations that support the notion that this strain could be useful as an animal model of depression. These abnormalities include increase in rapid eye movement sleep, decrease of saccharin consumption after stress, and reduced exploratory behavior in a novel open field. On the other hand, sexual behavior is a pleasure-seeking behavior that should be altered in a mood disorder characterized by anhedonia. In the present study, spontaneous masculine sexual behavior features were analyzed, both during 30-min tests as well as during a satiety test. Results showed that, compared to outbred Sprague-Dawley (SD) rats, both the FSL and the FRL rats displayed some behavioral impairment, like a marked decrease of the ejaculatory frequency. During the satiety tests, both the FSL and the FRL rats became exhausted sooner than their SD controls. In addition to considering the present results in terms of alterations in specific neurotransmitter systems, endogamy is proposed as a possible source of the behavioral alterations.

Effects of yohimbine and apomorphine on the male sexual behaviour pattern of the golden hamster (Mesocricetus auratus).

It has been reported that the copulatory pattern of male hamsters differs from that displayed by most rodents. Besides mount, intromission and ejaculatory patterns, male hamsters display a peculiar copulatory pattern known as long intromission (LI). This peculiar behavioural pattern emerges after the male has been allowed to ejaculate repeatedly. Although LIs have been linked to sexual exhaustion, their functional meaning and their pharmacological regulation have not yet been elucidated. In this study, the sexual behaviour pattern of male golden hamsters was analysed after the administration of yohimbine and apomorphine, drugs that selectively acts on the noradrenergic and dopaminergic system, respectively. Both drugs have proved effective in inducing facilitation of masculine sexual behaviour in several species, including rodents. Results showed that, as in rats, the administration of yohimbine and apomorphine in male hamsters seems to have a stimulatory effect on masculine sexual behaviour, although their effects differ in characteristics and in intensity. In particular, after yohimbine administration, the onset of LIs appears sooner than in control subjects and it seems that they are linked to the number of ejaculations. In addition, sexual activity seems increased after the onset of LIs, including an increase in ejaculations and in the number of LIs. On the other hand, apomorphine administration induced just a slight stimulatory effect limited to ejaculatory latency and postejaculatory interval. Concerning LIs, apomorphine induced a complete disappearance of LIs in 60% of the subjects. The full significance of these findings remains to be elucidated.

Further definition of the effect of corticosterone on the sleep-wake pattern in the male rat.

It is well known that the activation of the hypothalamic-pituitary-adrenal (HPA) axis can induce alterations in the sleep-wake pattern. Corticotropin-releasing factor (CRF), adrenocorticotropin, and corticosterone are involved in the activation of the axis and each one of them has shown an effect on wakefulness and sleep. Nevertheless, concerning corticosterone, the picture is still controversial. In the present study, we analyzed the effects of a low (LC, 0.2 mg), medium (MC, 2 mg), and high (HC, 4 mg) dose of corticosterone on the 24-h sleep cycle in rats. Results indicate that all doses produce an initial enhancement of wakefulness with a concomitant decrease of slow-wave sleep II (SWS II). This effect was observed within the first hour in all the doses but lasted until the third hour only after the higher doses. When plasma levels of corticosterone were analyzed by high-performance liquid chromatography (HPLC), the highest levels were observed during the first 3 h, which is coincident with an increase in the percentage of wakefulness. Nevertheless, when the overall percentage of the stages was analyzed, LC seemed to induce the opposite effect (decrease of wakefulness and increase of SWS II) than that induced by the two higher doses (increased wake time, decreased SWS II). Rapid eye movement (REM) sleep was not modified at any dose. These data indicate that corticosterone exerts an alerting effect that could be important in the initial stage of the stress response.