Preferencias condicionadas por sexo y drogas: Una comparación de las bases neurales

Objetivo. Realizar una comparación comportamental y neurobiológica de las preferencias condicionadas de pareja inducidas por sexo y las condicionadas por drogas en modelos de estudio llevados a cabo en animales de laboratorio. Desarrollo. Las preferencias condicionadas por sexo o por consumo de drogas tienen similitudes. En ambos procesos se aprende a asociar cambios de estado fisiológico y subjetivo a lo que se denomina recompensa con estímulos ambientales, induciendo así la formación de preferencias aprendidas, lo que ha llevado a pensar que tanto las preferencias de pareja que aparecen después de encuentros sexuales como el consumo repetido de drogas dependen, al menos en parte, del condicionamiento clásico que ocurre por la asociación de estímulos condicionados y la recompensa. Además, en ambos procesos se activan áreas cerebrales mesolímbicas que dependen de los mismos neurotransmisores, como la dopamina, los opioides y la oxitocina, entre otros. Agonistas de éstos facilitan el desarrollo de preferencias condicionadas y los antagonistas afectan a su desarrollo. Conclusiones. Los datos en animales experimentales sugieren que las preferencias condicionadas por drogas utilizan mecanismos cerebrales involucrados en la recompensa sexual. Dichos mecanismos se activan para detectar y aprender a buscar estímulos como los sexuales, importantes para la supervivencia y la reproducción

Reply to: Are stressful childhood experiences relevant in non monosexual women?

We thank the commentator for his thoughtful response (Schneeberger, 2015) to our study entitled, “Explaining Mental Health Disparities for Non-monosexual Women: Abuse History and Risky Sex, or the Burdens of Non-disclosure?” (Persson et al., 2014) To summarize, Schneeberger (2015) highlights three aspects of our methodological approach: (1) how the participants were grouped; (2) how sexual orientation was evaluated; and (3) how a history of childhood abuse was assessed. We will reflect on these three issues while further considering future research directions in the study of female sexual orientation and childhood abuse

Inhibition of lysine-specific demethylase enzyme disrupts sexually conditioned mate guarding in the female rat

Although female rats are typically described as having a promiscuous mating strategy, if sexually naïve females have their formative sexually rewarding experiences paired with the same male, they will recognize that male and display mate-guarding behavior towards him in the presence of a female competitor. Female rats that display mate guarding behavior also show enhanced activation of oxytocin and vasopressin neurons in the supraoptic and paraventricular hypothalamic nucleus. Here, we examined the potential role that histone demethylation might have in establishing this pair-bonded behavior, and whether the corresponding changes in oxytocin and vasopressin neuronal activation depended on demethylation. To accomplish this, we examined the effect of a lysine-specific demethylase-1 inhibitor to block the action of demethylase enzymes and maintain the methylation state of corresponding genes. Female rats treated with the demethylase inhibitor failed to show any measure of mate guarding, whereas females treated with vehicle displayed mate guarding behavior. Demethylase inhibitor treatment also blocked the ability of familiar male cues to activate oxytocin and vasopressin neurons, whereas vehicle-treated females showed this enhanced activation. These data indicate that histone demethylation is a crucial component in the epigenetic modification of neural circuitry that underlies conditioned mate guarding in female rats. These results are the first to demonstrate the role of histone demethylation underlying changes in mating strategy

Neurobiology of social attachments

Many types of social attachments can be observed in nature. We discuss the neurobiology of two types (1) intraspecific (with a partner) and (2) parental (with the offspring). Stimuli related to copulation facilitate the first, whereas pregnancy, parturition and lactation facilitate the second. Both types develop as consequence of cohabitation. These events seem to stimulate similar neural pathways that increase (1) social recognition, (2) motivation, reward; and (3) decrease fear/anxiety. Subregions of the amygdala and cortex facilitate social recognition and also disinhibition to decrease rejection responses. The interrelationship between MeA, BNST, LS may mediate the activation of NAcc via the mPOA to increase motivation and reward. Cortical areas such as the ACC discriminate between stimuli. The interaction between OT and D2-type receptors in NAcc shell facilitates intraspecific attachment, but D1-type appears to facilitate parental attachment. This difference may be important for maternal females to direct their attention, motivation and expression of attachment toward the appropriate target.Cuerpo Académico UV-CA-28 Neurociencias. Grant SEP-CONACYT (167773) to GACA

Persistent Genital Arousal Disorder (PGAD): case report of long-term symptomatic management with electroconvulsive therapy

Introduction. This is the second case report of a woman with bipolar disorder type I who noted the onset of persistent genital arousal disorder (PGAD) symptoms after abrupt cessation of paroxetine. With the worsening of PGAD symptoms, she developed severe depression and suicidal thoughts, resulting in her undergoing electroconvulsive therapy (ECT) as management. Aim. To describe a case of PGAD and develop hypotheses to explain the beneficial actions of ECT on PGAD based on 4 years of ECT administration. Methods. Patient self-report after obtaining consent, as well as literature review. Results. After the fourth ECT, the patient's PGAD symptoms abated serendipitously. She was placed on ECT on demand for the treatment of her PGAD. With each ECT treatment, PGAD symptoms immediately disappeared, relapsing slowly over time until the next ECT was administered. The patient has, thus far, received a total of 30 treatments of ECT. Side effects continue to be minimal and include brief short-term memory loss, headache, and muscle aches. Conclusion. ECT is known to induce cerebral excitatory and inhibitory neurotransmitter changes after acute and chronic administration. Sexual arousal is stimulated by the action of hypothalamic and limbic dopamine, noradrenaline, melanocortin, and oxytocin, and inhibited by serotonin, cerebral opioids, and endocannabinoids. Based on the patient's bipolar disorder, the mechanism of action of ECT and the observation of ECT effectiveness on her PGAD, we hypothesize the following: (i) bipolar disorder led to central hyperactive dopamine release, an important component in the pathophysiology of her PGAD; (ii) central serotonin deficiency after selective serotonin-reuptake inhibitor (SSRI) withdrawal resulted in a lack of inhibition of sexual excitement; (iii) ECT resulted in lowering of the hyperstimulated central dopamine release; and (iv) ECT led to an increase in sexual inhibition by stimulating serotonin activity

International Society for the Study of Women's Sexual Health (ISSWSH) review of epidemiology and pathophysiology, and a consensus nomenclature and process of care for the management of persistent genital arousal disorder/genito-pelvic dysesthesia (PGAD/GPD)

Background Persistent genital arousal disorder (PGAD), a condition of unwanted, unremitting sensations of genital arousal, is associated with a significant, negative psychosocial impact that may include emotional lability, catastrophization, and suicidal ideation. Despite being first reported in 2001, PGAD remains poorly understood. Aim To characterize this complex condition more accurately, review the epidemiology and pathophysiology, and provide new nomenclature and guidance for evidence-based management. Methods A panel of experts reviewed pertinent literature, discussed research and clinical experience, and used a modified Delphi method to reach consensus concerning nomenclature, etiology, and associated factors. Levels of evidence and grades of recommendation were assigned for diagnosis and treatment. Outcomes The nomenclature of PGAD was broadened to include genito-pelvic dysesthesia (GPD), and a new biopsychosocial diagnostic and treatment algorithm for PGAD/GPD was developed

Efficacy and safety of on-demand use of 2 treatments designed for different etiologies of female sexual interest/arousal disorder:3 Randomized Clinical Trials

Background In women, low sexual desire and/or sexual arousal can lead to sexual dissatisfaction and emotional distress, collectively defined as female sexual interest/arousal disorder (FSIAD). Few pharmaceutical treatment options are currently available. Aim To investigate the efficacy and safety of 2 novel on-demand pharmacologic treatments that have been designed to treat 2 FSIAD subgroups (women with low sensitivity for sexual cues and women with dysfunctional over-activation of sexual inhibition) using a personalized medicine approach using an allocation formula based on genetic, hormonal, and psychological variables developed to predict drug efficacy in the subgroups. Methods 497 women (21–70 years old) with FSIAD were randomized to 1 of 12 8-week treatment regimens in 3 double-blinded, randomized, placebo-controlled, dose-finding studies conducted at 16 research sites in the United States. Efficacy and safety of the following on-demand treatments was tested: placebo, testosterone (T; 0.5 mg), sildenafil (S; 50 mg), buspirone (B; 10 mg) and combination therapies (T 0.25 mg + S 25 mg, T 0.25 mg + S 50 mg, T 0.5 mg + S 25 mg, T 0.5 mg + S 50 mg, and T 0.25 mg + B 5 mg, T 0.25 mg + B 10 mg, T 0.5 mg + B 5 mg, T 0.5 mg + B 10 mg). Outcomes The primary efficacy measure was the change in satisfying sexual events (SSEs) from the 4-week baseline to the 4-week average of the 8-week active treatment period after medication intake. For the primary end points, the combination treatments were compared with placebo and the respective monotherapies on this measure. Results In women with low sensitivity for sexual cues, 0.5 mg T + 50 mg S increased the number of SSEs from baseline compared with placebo (difference in change [Δ] = 1.70, 95% CI = 0.57–2.84, P =.004) and monotherapies (S: Δ = 1.95, 95% CI = 0.44–3.45, P =.012; T: Δ = 1.69, 95% CI = 0.58–2.80, P =.003). In women with overactive inhibition, 0.5 mg T + 10 mg B increased the number of SSEs from baseline compared with placebo (Δ = 0.99, 95% CI = 0.17–1.82, P =.019) and monotherapies (B: Δ = 1.52, 95% CI = 0.57–2.46, P =.002; T: Δ = 0.98, 95% CI = 0.17–1.78, P =.018). Secondary end points followed this pattern of results. The most common drug-related side effects were flushing (T + S treatment, 3%; T + B treatment, 2%), headache (placebo treatment, 2%; T + S treatment, 9%), dizziness (T + B treatment, 3%), and nausea (T + S treatment, 3%; T + B treatment, 2%). Clinical Implications T + S and T + B are promising treatments for women with FSIAD. Strengths and Limitations The data were collected in 3 well-designed randomized clinical trials that tested multiple doses in a substantial number of women. The influence of T + S and T + B on distress and the potentially sustained improvements after medication cessation were not investigated. Conclusions T + S and T + B are well tolerated and safe and significantly increase the number of SSEs in different FSIAD subgroups. Tuiten A, van Rooij K, Bloemers J, et al. Efficacy and Safety of On-Demand Use of 2 Treatments Designed for Different Etiologies of Female Sexual Interest/Arousal Disorder: 3 Randomized Clinical Trials. J Sex Med 2018;15:201–216