Herlinda Bonilla-Jaime

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.

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.

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.

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

Abstract 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.

Oleamide and anandamide effects on food intake and sexual behavior of rats

Oleamide is a lipid with diverse properties, including cannabinoid-like activity. For example, it induces the classic triad of effects attributable to these molecules: decrease in core temperature, hypolocomotion, and reduction in pain perception. However, as it binds to the cannabinoid receptors (CB1) only at high concentrations, it is not considered an actual endocannabinoid. In this study, we tested the effect of oleamide on food intake and sexual behavior and compared it to the effect induced by anandamide. Results indicate that oleamide and anandamide increased food intake during the 3h post-injection. In addition, anandamide but not oleamide induced changes in sexual performance. This study further supports the role of endocannabinoids in food ingestion and male sexual behavior and gives additional support to the notion that, although oleamide might not be an endocannabinoid, it shares some effects with them.

Antidepressant effects of nicotine and fluoxetine in an animal model of depression induced by neonatal treatment with clomipramine

The association between smoking and depression has been widely investigated. Most of these reports suggest that nicotine (NIC) may act as an antidepressant. To examine the suggested antidepressant effect of nicotine and its possible interaction with the serotonergic system, we assessed the effect of nicotine and fluoxetine (FLX) in an animal model of depression induced by neonatal treatment with clomipramine (CLI) and submitted to the forced swim test (FST). Results corroborated that CLI-treated rats displayed higher levels of immobility. After the administration of nicotine (0.4 mg/kg sc) acutely (1 day), subchonically (7 days), and chronically (14 days), CLI-treated rats significantly reduced the immobility and increased swimming without affecting climbing. These effects were similar to the effects induced for subchronic and chronic administration of the antidepressant fluoxetine (5 mg/kg sc), a selective serotonin re-uptake inhibitor. However, fluoxetine failed to affect immobility when it was administered acutely. No synergism was observed when both drugs were administered simultaneously. The present results further corroborate the antidepressant action of nicotine and fluoxetine. The increase of swimming during the FST has been linked to an increase of serotonergic activity. Thus, it could be possible that the antidepressant action of nicotine is mediated by the serotonergic system.

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.

Lack of effect of corticosterone administration on male sexual behavior of rats.

The increase in plasma levels of corticosteroids as part of the stress response has been associated with failure in the reproductive function in most vertebrate species, both in females and males. Recently, we have shown that male sexual performance in rats is readily affected by different stressors, both acutely and chronically applied. However, there are few reports that directly correlate the increase in corticosteroid levels with the behavioral effects of stress. In this study we investigated whether the administration of corticosterone, either acutely or chronically, could reproduce the effects of stress on male sexual behavior in the male rat. Four doses of corticosterone (0.5, 1, 2, and 4 mg) or the vehicle, were administered during four consecutive days to sexually experienced males. Male sexual behavior was assessed after the first and the fourth injection. After the last test, males were killed and levels of corticosterone and testosterone were measured by HPLC. We observed an increase in corticosterone plasma levels in a dose-dependent manner. None of the sexual behavior parameters, however, was modified. Plasma levels of testosterone were not modified by corticosterone administration. Both steroids were increased in response to sexual activity, though. These data show that, unlike amphibians and female mammals, corticosteroids do not alter sexual behavior in male rats and suggest that the effect of stress on male sexual behavior cannot be explained by increases in corticosterone.

Linalool and β-pinene exert their antidepressant-like activity through the monoaminergic pathway

AIMS Linalool and β-pinene are two volatile monoterpenes that possess antidepressant-like activity. These are components of many aromatic plants used in folk medicine around the world to relieve anxiety and depression. In this contribution, we focused on examining the mechanism of action of these compounds. MAIN METHODS We used mice in the forced swimming test (FST) and antagonist drugs (i.p.) to receptors related to the depression process such as 5-HT1A. To assess the possible contribution of the serotoninergic system, animals were pre-treated with WAY 100635 (a 5-HT1A receptor antagonist) and PCPA (a serotonin synthesis inhibitor).To assess the participation of the noradrenergic system, the animals were pre-treated with yohimbine (an α2 receptor antagonist), propranolol (a β receptor antagonist) and neurotoxin DSP-4 (a noradrenergic neurotoxin). In the dopaminergic system, we used SCH23390 (a D1 receptor antagonist). KEY FINDINGS WAY 100635 blocked the antidepressant-like effect of linalool and β-pinene. In contrast, pretreatment of mice with PCPA did not modify reductions in the immobility time elicited by the two monoterpenes. The yohimbine modified the effect of linalool on immobility time. Propranolol and neurotoxin DSP-4 reversed the anti-immobility effect of β-pinene; also, SCH23390 blocked the antidepressant-like effect of β-pinene. SIGNIFICANCE Our results indicate that linalool and β-pinene produce an antidepressant-like effect through interaction with the monoaminergic system.

Effects of hormonal replacement with androgens and estrogens on male sexual behavior and plasma levels of these steroids in gonadectomized golden hamsters (Mesocricetus auratus)

Because the endocrine control of sexual behavior in male hamsters remains controversial, this study analyzed the influence of different androgens and estrogens in the regulation of masculine, sexual behavior (MBS). Aromatizable androgens: androstenedione (A) and testosterone (T), a non-aromatizable androgen: 5alpha-dihydrotestosterone (DHT), as well as estrogens (E2 and E1) alone or in combination with DHT, were administered in gonadectomized, sexually experienced males, for 3 weeks. In addition, plasma levels of these steroids were determined. Gonadectomy completely suppressed masculine sexual behavior (MSB) after 4 weeks. Both A and T replacements restored all the sexual behavior parameters in castrated hamsters by the 3rd week of treatment, with A being more potent in restoring all copulatory series and maintaining all MSB parameters, including long intromissions. Castrated males treated with DHT showed little interest in the female and did not display any copulatory behavior. Gonadectomized males treated with estrogens alone showed active anogenital investigation and displayed some mounts, but did not ejaculate. Males treated with estrogens combined with DHT had longer latencies and less number of ejaculations than males treated with aromatizable androgens. Long intromissions were observed only in males treated with T or A. Plasma levels of A were significantly higher than T levels in intact males. In males treated with A both androgens and estrogens were present in plasma. These results support the notion that aromatizable androgens, mainly A, but not non-aromatizable androgens or even estrogens in combination with DHT, play a relevant role in the endocrine regulation of MSB in the golden hamster.