RESUMEN
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.
Asunto(s)
Corticosterona/sangre , Naltrexona/farmacología , Antagonistas de Narcóticos/farmacología , Conducta Sexual Animal/efectos de los fármacos , Estrés Psicológico/sangre , Testosterona/sangre , Análisis de Varianza , Animales , Cromatografía Líquida de Alta Presión/métodos , Frío/efectos adversos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Electrochoque/efectos adversos , Masculino , Distribución Aleatoria , Ratas , Ratas Wistar , Tiempo de Reacción/efectos de los fármacos , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/etiología , Factores de TiempoRESUMEN
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.
Asunto(s)
Antidepresivos/administración & dosificación , Depresión/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Tagetes/química , Administración Oral , Animales , Antidepresivos/aislamiento & purificación , Antidepresivos/toxicidad , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Fluoxetina/farmacología , Masculino , Medicina Tradicional , México , Actividad Motora/efectos de los fármacos , Extractos Vegetales/toxicidad , Ratas , Ratas Wistar , Conducta Sexual Animal/efectos de los fármacos , NataciónRESUMEN
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.
Asunto(s)
Corticosterona/sangre , Conducta Sexual Animal/fisiología , Medio Social , Testosterona/sangre , Animales , Femenino , Masculino , Práctica Psicológica , Ratas , Ratas WistarRESUMEN
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.
Asunto(s)
Trastornos Mentales/metabolismo , Enfermedades del Sistema Nervioso/metabolismo , Nicotina/metabolismo , Receptores Nicotínicos/metabolismo , Sistema Nervioso Central/metabolismo , Humanos , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/fisiopatología , Estructura Molecular , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/fisiopatología , Agonistas Nicotínicos/química , Agonistas Nicotínicos/uso terapéutico , Isoformas de Proteínas/química , Isoformas de Proteínas/metabolismo , Subunidades de Proteína/química , Subunidades de Proteína/metabolismo , Receptores Nicotínicos/química , FumarRESUMEN
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.
Asunto(s)
Naltrexona/farmacología , Antagonistas de Narcóticos/farmacología , Sueño REM/efectos de los fármacos , Estrés Psicológico/psicología , Animales , Cromatografía Líquida de Alta Presión , Corticosterona/sangre , Inmovilización , Masculino , Ratas , Ratas Wistar , Fases del Sueño/efectos de los fármacos , Estrés Psicológico/etiologíaRESUMEN
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.
Asunto(s)
Corticosterona/sangre , Reproducción/fisiología , Conducta Sexual Animal/fisiología , Estrés Fisiológico/sangre , Testosterona/sangre , Enfermedad Aguda/psicología , Animales , Enfermedad Crónica/psicología , Inmovilización , Masculino , Ratas , Ratas Wistar , Estrés Fisiológico/psicologíaRESUMEN
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.
Asunto(s)
Corticosterona/sangre , Depresión/sangre , Estrés Fisiológico/sangre , Testosterona/sangre , Análisis de Varianza , Animales , Animales Recién Nacidos , Antidepresivos Tricíclicos/efectos adversos , Conducta Animal , Clomipramina/efectos adversos , Frío , Depresión/fisiopatología , Modelos Animales de Enfermedad , Femenino , Inmovilización , Masculino , Embarazo , Ratas , Ratas Wistar , Estrés Fisiológico/inducido químicamente , Estrés Fisiológico/fisiopatología , Natación , Factores de TiempoRESUMEN
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.
Asunto(s)
Antidepresivos Tricíclicos/farmacología , Clomipramina/farmacología , Corticosterona/sangre , Conducta Sexual Animal/efectos de los fármacos , Testosterona/sangre , Animales , Animales Recién Nacidos , Inmovilización , Masculino , Ratas , Ratas Wistar , Natación , Factores de TiempoRESUMEN
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.
Asunto(s)
Ritmo Circadiano , Corticosterona/sangre , Estrés Fisiológico/fisiopatología , Aumento de Peso , Enfermedad Aguda , Glándulas Suprarrenales/anatomía & histología , Animales , Enfermedad Crónica , Frío , Electrochoque , Inmersión , Cinética , Masculino , Tamaño de los Órganos , Ratas , Ratas Wistar , Restricción Física , Testículo/anatomía & histología , AguaRESUMEN
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.
Asunto(s)
Copulación , Sueño/fisiología , Vigilia , Animales , Encéfalo/metabolismo , Eyaculación/fisiología , Femenino , Masculino , Ratas , Ratas Wistar , Receptores de GABA/metabolismo , Serotonina/metabolismo , Sueño REM/fisiologíaRESUMEN
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.
Asunto(s)
Antiinflamatorios/farmacología , Corticosterona/farmacología , Fases del Sueño/efectos de los fármacos , Vigilia/efectos de los fármacos , Animales , Antiinflamatorios/sangre , Corticosterona/sangre , Masculino , Ratas , Ratas Wistar , Fases del Sueño/fisiología , Vigilia/fisiologíaRESUMEN
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.