Antidepressant-like activity of Tagetes lucida Cav. is mediated by 5-HT(1A) and 5-HT(2A) receptors.

It has been demonstrated that the aqueous extract of Tagetes lucida Cav. shows an antidepressant-like effect on the forced swimming test (FST) in rats. The aim of this study was to analyze the participation of the serotoninergic system in the antidepressant-like effect of the aqueous extract of T. lucida. Different doses of the extract of T. lucida were administered at 72, 48, 24, 18 and 1 h before FST. The animals were pretreated with a 5-HT1A receptor antagonist (WAY-100635, 0.5 mg/kg), a 5-HT2A receptor antagonist (ketanserin, 5 mg/kg), a ß-noradrenergic receptor antagonist (propranolol, 200 mg/kg), and with a α2-noradrenergic receptor antagonist (yohimbine, 1 mg/kg) alone or combined with the extract and pretreated with a serotonin synthesis inhibitor (PCPA) before treatment with 8-OH-DPAT + the extract of T. lucida. In addition, suboptimal doses of the 5-HT1A agonist (8-OH-DPAT) + non-effective dose of extract was analyzed in the FST. To determine the presence of flavonoids, the aqueous extract of T. lucida (20 µl, 4 mg/ml) was injected in HPLC; however, a quercetin concentration of 7.72 mg/g of extract weight was detected. A suboptimal dose of 8-OH-DPAT + extract of T. lucida decreased immobility and increased swimming and climbing. An antidepressant-like effect with the aqueous extract of T. lucida at doses of 100 and 200 mg/kg was observed on the FST with decreased immobility behavior and increased swimming; however, this effect was blocked by WAY-100635, ketanserin and PCPA but not by yohimbine and propranolol, suggesting that the extract of T. lucida could be modulating the release/reuptake of serotonin.

Orchiectomy modifies the antidepressant-like response of nicotine in the forced swimming test.

Several studies have demonstrated that nicotine (NIC) exhibits antidepressant-like effects. In addition, it has been suggested that sexual hormones participate in the antidepressant actions of antidepressives. The present study was designed to analyze the effect of orchiectomy and the supplementation of testosterone propionate (TP) or 17ß-estradiol (E(2)) on the antidepressant properties of NIC using the forced swimming test (FST), as well as to determine possible changes in the FST during different time periods after orchiectomy. In order to evaluate the influences of orchiectomy on the effects of NIC, the study first evaluated the effects of different time periods on orchiectomized rats (15, 21, 30, 45 and 60 days) that were subjected to the FST. Then, different doses of NIC (0.2, 0.4, 0.8, 1.6 mg/kg, sc) were administered for 14 days to both intact and orchiectomized rats (after 21 day) which were then also subjected to the FST. Finally, the influence of the TP or E(2) supplementation on the antidepressant-like effect of NIC on orchiectomized rats (after 21 days) was also analyzed. Results reveal that orchiectomy significantly increased immobility behavior and decreased swimming and climbing up to 60 days after castration. In contrast, NIC decreased immobility behavior and increased swimming in intact rats; whereas orchiectomy suppressed this antidepressant effect of NIC. Only with E(2) supplementation was it possible to restore the sensitivity of the castrated rats to NIC. These results suggest that E(2) was able to facilitate the antidepressant response of NIC in orchiectomized rats.

Circadian activity of corticosterone in an animal model of depression: response to muscarinic cholinergic stimulation.

Neonatal treatment with clomipramine (CMI) in rats induces multiple behavioral alterations during adulthood that resemble certain symptoms of human depression, such as impairments of pleasure-seeking behaviors. CMI may also induce permanent changes in the reactivity of the hypothalamic-pituitary-adrenocortical axis (HPA) to different stimuli; however, the endocrinal changes induced by this treatment are still a matter of debate. In the present study, we evaluated the levels of corticosterone in rats treated in the neonatal period with CMI in basal conditions (0, 6, 12 and 18 h after lights on) and after treatment with the antidepressant fluoxetine (FLX; 5mg/kg for 14 days). To evaluate the response of the HPA axis to a cholinergic agonist, we analyzed the effect of oxotremorine administration (OXO; 0.4, 0.8 mg/kg) on plasma levels of corticosterone. Administration of OXO took place at the beginning of each one of the two phases of the light-dark cycle (time points 0 and 12h, respectively). Results showed an increase in basal plasma levels of corticosterone in CMI-treated rats at time point zero and at 6h after the onset of the light period. While treatment with FLX reversed the increase in corticosterone plasma levels in CMI-treated rats, the results regarding cholinergic stimulation indicate that those rats do not respond to the administration of a low dose of OXO (0.4 mg/kg) at the onset of the dark phase (time point 12h). In conclusion, this study supports the hypothesis that neonatal treatment with CMI induces a hypersecretion of corticosterone in adulthood that was reversed through treatment with the antidepressant FLX. The CMI-treated rats showed a hyporesponse to cholinergic stimulation with OXO at low doses and at the beginning of the dark phase. Thus, the present results do not support the assumption that an increased sensitivity of the muscarinic cholinergic system is one of the possible correlates of the behavioral alterations seen in CMI-treated rats.

Naltrexone effects on male sexual behavior, corticosterone, and testosterone in stressed male rats.

Chronic physical or psychological stress disrupts male reproductive function. Studies in our laboratory have shown that stress by immersion in cold water (ICW) and by electrical foot shocks (EFS) has inhibitory effects on male sexual behavior; these effects do not seem to be mediated by an increase in corticosterone, nor by a decrease in testosterone. On the other hand, it is known that endogenous opioids are released in the brain in response to these same stressors; consequently, they could be participating in the impairment of sexual behavior, as well as in the changes in corticosterone and testosterone caused by stress. The aim of this study was to analyze the effects of the opioid antagonist naltrexone (NTX) on male sexual behavior, corticosterone, and testosterone in both stressed sexually experienced and naive male rats. Sexually experienced adult male rats were assigned to one of the following groups (n=10 each): 1) control group, males without sexual evaluation; 2) control group, rats injected ip with saline, non-stressed; 3) control group, rats injected with NTX (3 mg/kg) non-stressed; 4) rats injected ip with saline, and stressed by EFS; 5) rats injected ip with NTX (1.5 mg/kg) and stressed by EFS; 6) rats injected ip with saline and stressed by ICW; 7) rats injected ip with NTX (1.5 mg/kg) and stressed by ICW; 8) rats injected ip with NTX (3 mg/kg) and stressed by ICW. Naive males were assigned to the same control groups but only stressed by ICW and the NTX dose used was 3 mg/kg. Injections were given 30 min before stress sessions. Stress was applied on 20 consecutive days. Male sexual behavior was assessed 15 min after EFS or 30 min after ICW, on days 1, 4, 8, 12, 15, and 20. Trunk blood was collected at the end of the experiments on day 20 of stress. Corticosterone and testosterone were evaluated by HPLC. Mount, intromission and ejaculation latencies were longer in control saline naive males compared to control saline sexually experienced males on the first day. NTX administration to control naive males caused a decrease in mount, intromission, and ejaculation latencies, as well as an increase in ejaculatory frequency/30 min, compared to control-saline only on day 1. Stressed naive males showed higher mount, intromission and ejaculation latencies, compared to control and stressed sexually experienced males, as well as comparable increase in corticosterone and decrease in testosterone plasma levels. NTX administration before exposure to stress prevented the modifications caused by stress in sexual parameters. Sexual behavior in control sexually-active males injected with saline or NTX was not modified. Saline stressed males showed the previously reported alterations in sexual behavior, as well as an increase in corticosterone and a decrease in testosterone plasma levels. Stressed males injected with NTX before exposure to stress showed no alterations in male sexual behavior. NTX in control non-stressed males did not modify corticosterone plasma levels, but did cause a significant increase in plasma testosterone. The increase in corticosterone and the decrease in testosterone due to stress, were attenuated with the opioid antagonist, both in naive and sexually experienced males. Prevention of ICW stress effects was more effective with higher doses of NTX (3 mg/kg). These data suggest that endogenous opioids could be participating in the effects caused by stress on male sexual behavior, corticosterone, and testosterone.

Antidepressant-like effects of Tagetes lucida Cav. in the forced swimming test.

AIM OF THE STUDY: Tagetes lucida (Asteraceae), has been referred in Mexican traditional medicine for the treatment of different central nervous system (CNS) diseases, mainly depression. Nevertheless, the available scientific information about this species is scarce and there are no reports related to its possible effect on the CNS. In this work, the antidepressant-like effect of extract of Tagetes lucida was evaluated in rats, as well as its potential adverse effects on male sexual behavior (MSB). MATERIALS AND METHODS: Antidepressant activity was studied using forced swimming test (FST), motor activity in the open-field test and on MSB in sexually experienced male. The aqueous extract of Tagetes lucida in doses of 5, 10, 50, 100 and 200mg/(kgday)(-1) were administered orally for 14 consecutive days and evaluated on day 14, 2h after the last dose treatment. Fluoxetine (10mg/(kgday)(-1), p.o.) was used as the control positive. RESULTS: The aqueous extract (10, 50, 100mg/(kgday)(-1)) significantly reduced immobility and increased swimming without affecting climbing behavior in the FST. These same doses were not able to modify neither the motor activity nor the MSB. CONCLUSION: These data indicate that the extract of Tagetes lucida possesses antidepressant-like properties in rats.

Hormonal responses to different sexually related conditions in male rats.

Plasma levels of corticosterone (C) and testosterone (T) increase after sexual activity in males of several species. However, the physiological significance of these increases has not been elucidated. In the present study, hormonal response to different conditions linked to sexual activity was assessed. In the first experiment, plasma levels of C and T were assessed both in sexually experienced and naive male rats after the following conditions: (A) control group, without sexual stimulation; (B) males exposed to ovariectomized females; (C) males exposed to intact, non-receptive females; (D) males exposed to receptive females with the vagina obstructed, to avoid intromission; (E) males exposed to receptive females: but separated by a grid that prevents physical contact; (F) males exposed to receptive females during 30 min. In a second experiment, experienced male rats were allowed to repeatedly copulate until reaching the criteria for sexual exhaustion, and 24 h later, they were allowed to copulate. Once sexually related conditions ended, males were killed and their blood was obtained. C and T plasma levels were assessed by HPLC with ultraviolet (UV) detection. Results indicate that T did not increase significantly in naive male in any sexual condition, while in the experienced males, significant increases were observed with the mere presence of a receptive female and also after ejaculation. These increases were significantly larger in experienced males. On the other hand, C also increased in all sexual conditions, both in experienced and naive rats; however, the increase observed was larger in experienced males. Regarding sexual satiety, both C and T increased after copulating ad libitum to satiety. T increased almost three-fold compared to control, while C increased two-fold. No significant changes were observed in either one of the steroids 24 h after sexual exhaustion, even though males remained with a receptive female during an hour. These results show that sexual experience has an important influence on the hormonal response to sexual activity. C rises could be directly related to sexual arousal involved in the different sexual conditions, while T rises seem to have a direct relationship with both the motivation and execution aspects of masculine sexual behavior.

[Nicotine acetylcholine receptors and neuropsychiatric disorders]. / Receptores nicotínicos cerebrales y trastornos neuropsiquiátricos.

OBJECTIVES: This review will be attempt to describe the current knowledge on the neuronal nicotinic acetylcholine receptors (nAChRs) and their involvement in the pathogenesis of a number of neuropsychiatric disorders and the properties of recently synthesized subtype-selective nAChRs. The potential brain therapeutic targets for nAChRs are reviewed. DEVELOPMENT: The nAChRs belong to a family of ligand-gated channels which are widely distributed in brain. Multiple subtypes of these receptors exist, each with diverse structures, individual pharmacological and functional properties. In contrast to the muscular nAChRs, the physiological functions of nAChRs are not well defined to date. In addition, the majority of evidence defining potential therapeutic targets involving nAChRs has resulted from studies on the effects of nicotine in a variety of preclinical and, to a lesser extent, clinical models. The preclinical research continues to focus on nicotine and a number of novel nAChRs agonists have been synthesized in the last few years that may have therapeutic potential in a number of neurological and psychiatric conditions. CONCLUSIONS: The structure of nAChRs and the considerable molecular diversity in subunits offers the possibility of a large number of nAChRs subtypes, which, based on pharmacological precedent, may serve a variety of discrete functions within the brain and thus represent novel targets for therapeutic agents. A promising trend for therapy is the synthesis of new agonists with high nAChRs subtype selectivity, which do not exhibit nicotine's side effects and do show clear beneficial actions in the neuropsychiatric disorders.

Receptores nicotínicos cerebrales y trastornos neuropsiquiátricos / Nicotine acetylcholine receptors and neuropsychiatric disorders

Objetivos. En esta revisión se pretende describir los conocimientos actuales de los receptores neuronales nicotínicos de la acetilcolina (nAChR) y su implicación en la patogénesis de diversos trastornos neuropsiquiátricos, así como las propiedades de los recién sintetizados nAChR de subtipo selectivo. Se revisan también los posibles blancos terapéuticos cerebrales para los nAChR. Desarrollo. Existen múltiples tipos de estos receptores, cada uno con diversas estructuras y unas propiedades farmacológicas y funcionales individuales. En contraste con los nAChR musculares, las funciones fisiológicas de los nAChR aún no han sido bien definidas. Además, la mayor parte de los datos que definen los posibles blancos terapéuticos que implican los nAChR provienen de estudios sobre los efectos de la nicotina en varios modelos preclínicos y, aunque en menor grado, clínicos. Las investigaciones preclínicas siguen centrándose en la nicotina y en los últimos años se han sintetizado diversos agonistas nuevos de los nAChR que podrían tener un valor terapéutico potencial en diversas patologías neurológicas y psiquiátricas. Conclusiones. La estructura de los nAChR y la elevada diversidad molecular en las subunidades facilitan la posibilidad de que exista un gran número de subtipos de nAChR, que, en base a los precedentes farmacológicos, pueden desempeñar diversas funciones discretas en el cerebro y por lo tanto representar blancos nuevos para las sustancias terapéuticas. Una tendencia esperanzadora en la terapéutica es la síntesis de nuevos agonistas con un elevado grado de selectividad de subtipos de nAChR, los cuales no parecen tener los efectos adversos de la nicotina y sí que exhiben una actividad beneficiosa clara en los trastornos neuropsiquiátricos (AU)

Objectives. This review will be attempt to describe the current knowledge on the neuronal nicotinic acetylcholine receptors (nAChRs) and their involvement in the pathogenesis of a number of neuropsychiatric disorders and the properties of recently synthesized subtype-selective nAChRs. The potential brain therapeutic targets for nAChRs are reviewed. Development. The nAChRs belong to a family of ligand-gated channels which are widely distributed in brain. Multiple subtypes of these receptors exist, each with diverse structures, individual pharmacological and functional properties. In contrast to the muscular nAChRs, the physiological functions of nAChRs are not well defined to date. In addition, the majority of evidence defining potential therapeutic targets involving nAChRs has resulted from studies on the effects of nicotine in a variety of preclinical and, to a lesser extent, clinical models. The preclinical research continues to focus on nicotine and a number of novel nAChRs agonists have been synthesized in the last few years that may have therapeutic potential in a number of neurological and psychiatric conditions. Conclusions. The structure of nAChRs and the considerable molecular diversity in subunits offers the possibility of a large number of nAChRs subtypes, which, based on pharmacological precedent, may serve a variety of discrete functions within the brain and thus represent novel targets for therapeutic agents. A promising trend for therapy is the synthesis of new agonists with high nAChRs subtype selectivity, which do not exhibit nicotine’s side effects and do show clear beneficial actions in the neuropsychiatric disorders (AU)

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.

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.

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.

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.

Effect of electric foot shocks, immobilization, and corticosterone administration on the sleep-wake pattern in the rat.

Knowledge concerning the impact of stressful situations on the sleep-wake pattern has been growing rapidly in the last decade. Immobilization (IMB) in rats elicits a significant increase of rapid eye movement (REM) sleep during the following 10 h. Participation of the adrenergic system has been clearly shown in this effect. On the other hand, it is well known that the time of the circadian cycle in which the stressor is applied could influence the results. It is also well known that the activation of the hypothalamic-pituitary-adrenal (HPA) axis, the release of corticosterone (COR), and the activation of the adrenergic and of the opioidergic systems are the most evident effects of stress. In the present study, we analyzed the effects of two stressors, IMB and electric foot shocks (EFS), on 24 h of continuous sleep recordings. These stressors were applied immediately before the onset of the light period. COR was also administered in an attempt to replicate the stressor-induced effects. Adult, male Wistar rats were chronically implanted for sleep recording, and after a recovery period and a 24-h basal sleep recording, they were submitted to EFS, COR, and IMB. A 10-day period elapsed between each treatment, and all of them were applied during the last moments of the dark phase of the light cycle. Results showed that IMB increased the percentage of REM sleep (83.7%) and slow-wave sleep II (SWS II; 17.3%) mainly during the dark phase (i.e., after 12 h), while EFS and COR administration elicited only slight and transient changes in the sleep-wake pattern. These data suggest that IMB applied to rats at the end of the dark cycle is effective in producing a sleep-elevating response, although this effect is enhanced during the dark phase. It seems, however, that not all the stressful situations are capable of eliciting this sleep-promoting effect, and also that COR release does not mediate this response.