Resolution of sexual dysfunction during acute treatment of major depression with milnacipran

Objective The sexual function and enjoyment questionnaire (SFEQ) was developed to assess and detect changes in sexual function in men and women. The aim of the present study was to use the SFEQ to evaluate the effects of the serotonin-noradrenaline reuptake inhibitor, milnacipran, in the treatment of depression in two culturally different populations. Methods The SFEQ was employed in two studies investigating milnacipran in the treatment of major depression: a 12-week open study in Brazil and a 6-week randomised controlled study in Europe. Results At endpoint, 61.3% (Brazil) and 78.4% (Europe) of patients had >= 50% reduction of baseline Hamilton Depression Rating (HAMD) score. All SFEQ items showed improvements in sexual function in both Studies at endpoint, 60% (Brazil) and 56% (Europe) of patients stating that their Sexual desire was as great as or greater than it had been before their depressive episode. Conclusions Milnacipran appears to improve sexual function in parallel with improvement in other symptoms of depression. The SFEQ is a sensitive instrument for measuring changes in sexual function and appears to be unaffected by Cultural differences as shown by similar findings in Brazil and Europe. Copyright (C) 2008 John Wiley & Sons, Ltd.

STIM and Orai proteins: players in sexual differences in hypertension-associated vascular dysfunction?

Sex-associated differences in hypertension have been observed repeatedly in epidemiological studies; however, the mechanisms conferring vascular protection to females are not totally elucidated. Sex-related differences in intracellular Ca(2+) handling or, more specifically, in mechanisms that regulate Ca(2+) entry into vascular smooth muscle cells have been identified as players in sex-related differences in hypertension-associated vascular dysfunction. Recently, new signalling components that regulate Ca(2+) influx, in conditions of intracellular store depletion, were identified: STIM1 (stromal interaction molecule 1), which works as an intracellular Ca(2+) sensor; and Orai1, which is a component of the CRAC (Ca(2+) release-activated Ca(2+)) channels. Together, these proteins reconstitute store-operated Ca(2+) channel function. Disturbances in STIM1/Orai1 signalling have been implicated in pathophysiological conditions, including hypertension. In the present article, we analyse evidence for sex-related differences in Ca(2+) handling and propose a new hypothesis where sex-related differences in STIM/Orai signalling may contribute to hypertension-associated vascular differences between male and female subjects.

Glutamatergic Antagonism in the NTS Decreases Post-Inspiratory Drive and Changes Phrenic and Sympathetic Coupling During Chemoreflex Activation

Costa-Silva JH, Zoccal DB, Machado BH. Glutamatergic antagonism in the NTS decreases post-inspiratory drive and changes phrenic and sympathetic coupling during chemoreflex activation. J Neurophysiol 103: 2095-2106, 2010. First published February 17, 2010; doi: 10.1152/jn.00802.2009. For a better understanding of the processing at the nucleus tractus solitarius (NTS) level of the autonomic and respiratory responses to peripheral chemoreceptor activation, herein we evaluated the role of glutamatergic neurotransmission in the intermediate (iNTS) and caudal NTS (cNTS) on baseline respiratory parameters and on chemoreflex-evoked responses using the in situ working heart-brain stem preparation (WHBP). The activities of phrenic (PND), cervical vagus (cVNA), and thoracic sympathetic (tSNA) nerves were recorded before and after bilateral microinjections of kynurenic acid (Kyn, 5 nmol/20 nl) into iNTS, cNTS, or both simultaneously. In WHBP, baseline sympathetic discharge markedly correlated with phrenic bursts (inspiration). However, most of sympathoexcitation elicited by chemoreflex activation occurred during expiration. Kyn microinjected into iNTS or into cNTS decreased the postinspiratory component of cVNA and increased the duration and frequency of PND. Kyn into iNTS produced no changes in sympathoexcitatory and tachypneic responses to peripheral chemoreflex activation, whereas into cNTS, a reduction of the sympathoexcitation, but not of the tachypnea, was observed. The pattern of phrenic and sympathetic coupling during the chemoreflex activation was an inspiratory-related rather than an expiratory-related sympathoexcitation. Kyn simultaneously into iNTS and cNTS produced a greater decrease in postinspiratory component of cVNA and increase in frequency and duration of PND and abolished the respiratory and autonomic responses to chemoreflex activation. The data show that glutamatergic neurotransmission in the iNTS and cNTS plays a tonic role on the baseline respiratory rhythm, contributes to the postinspiratory activity, and is essential to expiratory-related sympathoexcitation observed during chemoreflex activation.

Sexual differentiation of cortical spreading depression propagation after acute and kindled audiogenic seizures in the Wistar audiogenic rat (WAR)

Brain excitability diseases like epilepsy constitute one factor that influences brain electrophysiological features. Cortical spreading depression (CSD) is a phenomenon that can be altered by changes in brain excitability. CSD propagation was presently characterized in adult mate and female rats from a normal Wistar strain and from a genetically audiogenic seizure-prone strain, the Wistar audiogenic rat (WAR), both previously submitted (RAS(+)), or not (RAS(-)), to repetitive acoustic stimulation, to provoke audiogenic kindling in the WAR-strain. A gender-specific change in CSD-propagation was found. Compared to seizure-resistant animals, in the RAS- condition, mate and female WARs, respectively, presented CSD-propagation impairment and facilitation, characterized, respectively, by lower and higher propagation velocities (P<0.05). In contraposition, in the RAS(+) condition, mate and female WARs displayed, respectively, higher and tower CSD-propagation rates, as compared to the corresponding controls. In some Wistar and WAR females, we determined estrous cycle status on the day of the CSD-recording as being either estrous or diestrous; no cycle-phase-related differences in CSD-propagation velocities were detected. In contrast to other epilepsy models, such as Status Epilepticus induced by pilocarpine, despite the CSD-velocity reduction, in no case was CSD propagation blocked in WARs. The results suggest a gender-related, estrous cycle-phase-independent modification in the CSD-susceptibility of WAR rats, both in the RAS(+) and RAS(-) situation. (C) 2008 Elsevier B.V. All rights reserved.

Increased cardiac sympathetic drive and reduced vagal modulation following endothelin receptor antagonism in healthy conscious rats

1. The present study evaluated changes in autonomic control of the cardiovascular system in conscious rats following blockade of endothelin (ET) receptors with bosentan. 2. Rats were treated with bosentan or vehicle (5% gum arabic) for 7 days by gavage. 3. Baseline heart rate (HR) was higher in the bosentan-treated group compared with the control group (418 +/- 5 vs 357 +/- 4 b.p.m., respectively; P < 0.001). This baseline tachycardia was associated with a lower baroreflex sensitivity of the bradycardiac and tachycardiac responses in the bosentan-treated group compared with the control group. Sequential blockade of the parasympathetic and sympathetic autonomic nervous system with methylatropine and propranolol showed a higher intrinsic HR in the bosentan-treated group compared with the control group (411 +/- 5 vs 381 +/- 4 b.p.m., respectively; P < 0.05). This was accompanied by a higher cardiac sympathetic tone (31 +/- 1 vs 13 +/- 1%, respectively; P < 0.01) and a lower vagal parasympathetic tone (69 +/- 2 vs 87 +/- 2%, respectively; P < 0.01) in the bosentan-treated group compared with the control group. Variance and high-frequency oscillations of pulse interval (PI) variability in absolute and normalized units were lower in the bosentan-treated group than in the control group. Conversely, low-frequency (LF) oscillations of PI variability in absolute and normalized units, as well as variance and LF oscillations of systolic arterial pressure variability, were greater in the bosentan-treated group than the control group. 4. Overall, the data indicate an increased cardiac sympathetic drive, as well as lower vagal parasympathetic activity and baroreflex sensitivity, in conscious rats after chronic blockade of ET receptors with bosentan.

Evaluation of Sexual Function in Brazilian Pregnant Women

The objective of the present study was to evaluate the sexual function of pregnant women and to identify the potential variables associated with it. The study was conducted on 137 low-risk, sexually active pregnant women who filled out the Female Sexual Function Index (FSFI) questionnaire. Although 61% of the women assessed presented an FSFI score 26.5, they declared that they were satisfied with the emotional proximity to their partner, with their relationship, and with their sex life. A positive association was detected between sexual dysfunction and gestational age and a report of urinary incontinence and excessive weight gain in the current pregnancy.

Sexual Dysfunction Treatment in a Patient With Mullerian Agenesy Submitted to Neovaginoplasty: A Case Report

Vagina agenesis is a rare entity. Mayer-Rokitansky-Kuster-Hauser syndrome is the most significant cause of vagina agenesis, whereas the second most common cause is complete androgen syndrome. Surgical treatment can propitiate a vaginal reconstruction, but sexual function depends on several factors that affect sexual performance. Many reports focus on the intraoperative and postoperative results and only describe the global approach to these patients, but reports focusing on the management of these patients to enable them to have a normal sexual life are lacking. This case report highlights a multidisciplinary treatment for this kind of morbidity and emphasizes the necessity of incorporating careful attention to sexual health in the treatment of these patients so that they may achieve a good therapeutic response, resulting in a pleasurable sexual life and a good quality of living.

Prenatal Lipopolysaccharide Exposure Affects Maternal Behavior and Male Offspring Sexual Behavior in Adulthood

Objective: This study investigates the effects of prenatal lipopolysaccharide (LPS) exposure on the maternal behavior of pregnant rats and the physical development and sexual behavior of their male offspring in adulthood. Methods: For two experiments, pregnant rats were injected with LPS (250 mu g/kg, i.p.) on gestation day (GD) 21. In the first experiment, the maternal behavior (postnatal day, PND, 6) and the dam`s open-field general activity (PND7) were evaluated. In the second experiment, the maternal pre- and postnatal parameters, the pup`s development, the offspring`s sexual behavior in adulthood, and the pup`s organ weights were assessed. Results: Compared to the control group, the LPS-treated dams presented reduced maternal behavior, decreased general activity, a smaller body weight difference between GD21 and PND1, a greater number of perinatal deaths, and smaller litters. For the male pups, LPS treatment resulted in a decreased body weight on PND2, whereas the anogenital distance and the day of testis descent were not modified. The male sexual behavior was impaired by prenatal LPS. Particularly the number of ejaculating animals was reduced. The testis weight was also lower in the prenatally LPS-treated rats than in the control rats. Conclusion: We propose that prenatal LPS exposure on GD21 acts as an imprinting factor that interferes with the programming of brain sexual determination in offspring. Copyright (C) 2009 S. Karger AG, Basel

Ivermectin impairs sexual behavior in sexually naive, but not sexually experienced male rats

Ivermectin (IVM) is an antiparasitic drug, widely used in domestic animals. In mammals, IVM act as a GABA agonist. This neurotransmitter has an important role in the regulation of sexual behavior. Thus, this study sought to investigate the effects of various medically relevant doses IVM on the sexual behavior of male rats. In particular, we also wished to examine if previous sexual experience modulated responses to IVM. In the first experiment, the sexual behavior of inexperienced male rats was analyzed after they received 0.2, 0.6, 1.0 or 2.0 mg/kg IVM, 15 mm prior to behavioral testing. In the second experiment, the effects of four previous sexual experiences on IVM treated rats (1.0 or 2.0 mg/kg, 15 min prior to the 5th session) were assessed. The standard therapeutic dose (0.2 mg/kg) did not impair the sexual behavior of inexperienced male rats. At a more concentrated dose (0.6 mg/kg), which is still within the therapeutic range, the appetitive phase of sexual behavior of inexperienced male rats was impaired. Likewise, 1.0 mg/kg impaired the appetitive phase. Previous sexual experience blocked almost entirely this sexual impairment, suggesting that previous sexual experience exerts a positive effect in attenuating the sexual impairment produced by IVM treatment. Therefore, the standard therapeutic dose of IVM can be used without producing side effects on sexual behavior. Use of more concentrated therapeutic doses is not recommended during reproductive periods, unless the animals have had previous sexual experience. (C) 2010 Elsevier Ltd. All rights reserved.

Moxidectin interference on sexual behavior, penile erection and hypothalamic GABA levels of male rats

The moxidectin (MXD) is an antiparasitic drug used in domestic animals. The mechanism of action, in mammals, involves GABA, a neurotransmitter with an important role in the sexual behavior control. Presently, the effects of 0.2 mg/kg therapeutic dose were studied on sexual behavior, sexual motivation, penile erection and central GABA levels. Sexual behavior results showed increased latencies to the first mount and intromission as well as in inter-intromission interval; a reduction in total mounts was detected on the drug post-treatment. No difference was observed between sexual motivation of control and experimental animals. MXD treatment reduced penile erection and hypothalamic GABA levels. The results suggest that MXD reduced sexual behavior and penile erection by an action on the hypothalamic GABA system. Probably, the lack of effects in the motivational test and the increased mount and intromission latencies as well as decreased total mounts could be explained as a consequence of reduced male rat erection process. (C) 2007 Elsevier Ltd. All rights reserved.