Couples' Use of Online Stress Management and Resiliency Training for Sexual Health Concerns: A Randomized Controlled Trial.

INTRODUCTION: Mindfulness is a promising intervention for female sexual dysfunction (FSD); however, of the mindfulness interventions studied, few treat the woman and her partner. AIM: We developed a brief online mindfulness, resilience, and psychoeducation intervention, Stress Management and Resiliency Training for Sexuality (Sex SMART), for women with sexual health concerns and their partners. METHODS: Women with female sexual interest/arousal disorder and their partners were recruited between February 24, 2015, and October 6, 2016, and randomized to treatment or control groups (received educational pamphlets). The treatment intervention comprised of an online SMART and sexual health psychoeducation module. MAIN OUTCOME MEASURES: The Female Sexual Function Index (FSFI), Female Sexual Distress Scale-Revised (FSDS-R), Sexual Desire Inventory-2 (SDI-2), Revised Dyadic Adjustment Scale (RDAS), International Index of Erectile Function (IIEF), and other subjective measures were used to assess sexual function and sexual distress at baseline and 12 weeks. RESULTS: The study included 60 women and their partners (30 couples in each group). In both groups, sexual function by total FSFI scores and sexual distress scores significantly improved at 12 weeks compared with baseline, with no significant between-group differences (FSFI effect estimate for Sex SMART vs control = +1.4 (90% CI [-0.6 to +3.4]; P=.13). Both participants and partners randomized to the intervention reported significantly improved attitude and feelings, comfort as a sexual person, and subjective sexual functioning at 12 weeks. The findings provide preliminary evidence for efficacy of an online intervention for couples with sexual health problems. CONCLUSIONS: A brief online mindfulness, resilience, and psychoeducation-based intervention showed no significant improvement in many outcomes (FSFI, FSDS-R, SDI-2, RDAS) of sexual health versus controls. Although this is the first online randomized controlled trial to evaluate a mindfulness-based therapy intervention, it was limited by its lack of population diversity and high attrition rate. Significant improvements in subjective sexual health and partner sexual function by the International Index of Erectile Function were reported only in the intervention group. Rullo JE, Sood R, Fokken SC, et al. Couples' Use of Online Stress Management and Resiliency Training for Sexual Health Concerns: A Randomized Controlled Trial. Sex Med 2021;9:100404.

Chronic stress in adolescence differentially affects cocaine vulnerability in adulthood in a selectively bred rat model of individual differences: role of accumbal dopamine signaling.

Stress during adolescence has profound effects on the onset and severity of substance use later in life. However, not everyone with adverse experiences during this period will go on to develop a substance use disorder in adulthood, and the factors that alter susceptibility to substance use remain unknown. Here, we investigated individual differences in response to stress and drugs of abuse using our selectively bred high-responder (bHR) and low-responder (bLR) rats. These animals model extremes of temperamental tendencies and differ dramatically in both stress responsiveness and addiction-related traits. The present study investigated how environmental interventions in the form of a chronic variable stress (CVS) regimen in early adolescence interact with the bHR/bLR phenotype to alter behavioral sensitization to cocaine in adulthood. We also determined whether accumbal dopamine signaling is involved in the interaction of stress history and cocaine by assessing the mRNA levels of dopamine D1 (D1R) and D2 (D2R) receptors. Our results showed that CVS history alone had enduring and phenotype-specific effects on accumbal dopamine signaling. Importantly, adolescent stress had opposing effects in the two lines- decreasing the locomotor response to cocaine challenge in bHRs but increasing this measure in bLRs. Moreover, these opposing effects on cocaine sensitivity following adolescent CVS were accompanied by parallel effects in the accumbal dopamine system, with prior stress and cocaine exposure interacting to decrease D2R mRNA in bHRs but increase it in bLRs. Overall, these findings indicate that environmental challenges encountered in adolescence interact with genetic background to alter vulnerability to cocaine later in life.Lay SummaryStress experienced during adolescence affects the onset and severity of drug dependence later in life. However, not everyone with adverse experiences during this period will go on to develop SUD in adulthood. Using a rat model of innate differences in emotional reactivity, this study shows that the interplay between individual temperament and previous experience of adolescent stress/trauma determines whether an individual will be vulnerable or resilient to develop SUDs later in life. In addition, the present study shows that the dopamine D2 receptor in the brain's reward center, nucleus accumbens, may be implicated in this interplay.

Biopsychosocial Management of Female Sexual Dysfunction: A Pilot Study of Patient Perceptions From 2 Multi-Disciplinary Clinics.

BACKGROUND: Sexual dysfunction is often complex and biopsychosocial. Traditional sexual health care management involves individual providers not in a multi-disciplinary setting. A multi-disciplinary team may consist of a medical provider, pelvic floor physical therapist, and sex therapist. AIM: The aim was to explore the patient perceptions of benefit from management of their sexual dysfunction by a biopsychosocial multi-disciplinary team. METHODS: A survey was e-mailed to women patients seen by multi-disciplinary teams at 2 different settings: San Diego Sexual Medicine or Mayo Clinic Women's Health Clinic during a 27-month period. Data are reported using summary statistics for age and count for remaining survey responses. Cochran-Armitage tests for trend were used to compare pre- and post-comfort levels. OUTCOMES: Main outcome measures included perceived benefit of being managed in a team-based model of care, level of benefit and satisfaction from each provider, and difference from pre-conceived level of comfort to actual comfort after each provider visit. RESULTS: 89 of 270 e-mailed surveys were analyzed. Patient populations (mean age 47.6, range 23-77 years) were similar between sites. Overall, 82% of respondents reported moderate/great benefit from the team-based model; 72.1% reported management by all 3 providers valuable/extremely valuable; and 84.3% were somewhat/very satisfied with the model. Women endorsed specific ways in which they benefitted from the team-based model including: improved sexual function (58.1%), feeling validated (72.1%) and listened to (62.8%), that they better understood their health concerns (65.1%), that their partner better understood their health concerns (46.5%), and feeling normal (46.5%). There were no significant differences between the 2 clinics in terms of patient-perceived benefit, value, or satisfaction. CONCLUSIONS: The team-based model of care for management of sexual dysfunction in women including a medical provider, physical therapist, and sex therapist is associated with patient-perceived benefit, satisfaction, and value. Rullo J, Faubion S, Hartzell R, et al. Biopsychosocial Management of Female Sexual Dysfunction: A Pilot Study of Patient Perceptions From 2 Multi-Disciplinary Clinics. Sex Med 2018;6:217-223.

Maladaptive Sexual Behavior Following Concurrent Methamphetamine and Sexual Experience in Male Rats is Associated with Altered Neural Activity in Frontal Cortex.

The use of psychostimulants is often associated with hypersexuality, and psychostimulant users have identified the effects of drug on sexual behavior as a reason for further use. It was previously demonstrated in male rats that methamphetamine (Meth), when administered concurrently with sexual behavior results in impairment of inhibition of sexual behavior in a conditioned sex aversion (CSA) paradigm where mating is paired with illness. This is indicative of maladaptive sex behavior following Meth and sex experience. The present study examined the neural pathways activated during inhibition of sexual behavior in male rats and the effects of concurrent Meth and sexual behavior on neural activity, using ERK phosphorylation (pERK). First, exposure to conditioned aversive stimuli in males trained to inhibit sexual behavior in the CSA paradigm increased pERK expression in medial prefrontal (mPFC), orbitofrontal cortex (OFC) and areas in striatum and amygdala. Second, effects of concurrent Meth and sex experience were tested in males that were exposed to four daily sessions of concurrent Meth (1 mg/kg) or saline and mating and subsequently exposed to CSA one week after last treatment. Meth and mating-treated males showed significant impairment of inhibition of mating, higher pERK expression under baseline conditions, and disrupted pERK induction by exposure to the conditioned aversive stimuli in mPFC and OFC. These alterations of pERK occurred in CaMKII-expressing neurons, suggesting changes in efferent projections of these areas. Altogether, these data show that concurrent Meth and mating experience causes maladapative sexual behavior that is associated with alterations in neural activation in mPFC and OFC.

Revealing a latent variable: individual differences in affective response to repeated injections.

[Correction Notice: An Erratum for this article was reported in Vol 129(5) of Behavioral Neuroscience (see record 2015-43762-001). In the article, there was an error in the abstract. The sentence "However, injections significantly increased time spent immobile in the forced swim test in LRs, while the identical regimen significantly decreased the same measure in HRs, compared with handled-controls." should be "However, injections significantly increased time spent immobile in the forced swim test in HRs, while the identical regimen significantly decreased the same measure in LRs, compared with handled-controls."] Latent variables may exist in experimental designs and may interfere with reproducibility of findings. The present study reveals 1 such variable, the individual differences in affective response to chronic injection stress, by using the novelty-seeking phenotype as a model of differential emotional reactivity. The phenotype is identified by exposing a population of experimentally naïve outbred rats to the mild stress of a novel environment and classifying them as high responders (HR; upper 1/3) and low responders (LR; lower 1/3) based on their locomotor reactivity. Research has shown that HR/LR animals differ in their basal levels of anxiety- and depressive-like behavior, as well as in their response to environmental and pharmacological challenges; suggesting validity of this model in studying individual differences in stress reactivity. The present data showed that 14 daily, intraperitoneal saline injections did not alter the phenotypic differences in social behavior observed basally in HR/LR rats. However, injections significantly increased time spent immobile in the forced swim test in HRs, [corrected] while the identical regimen significantly decreased the same measure in LRs, [corrected] compared with handled-controls. These data indicate that individual differences in stress reactivity can have a significant impact on the depressive-like responses to repeated intraperitoneal injections in rats. Given that such underlying emotional variability exists within standard, outbred rat populations, this study highlights the importance of accounting for such variability in any study investigating the effects of repeated drug administration on depressive-like behavior for reliability and replicability of findings. Thus, we recommend including an uninjected control group in all studies.

Endogenous opioid-induced neuroplasticity of dopaminergic neurons in the ventral tegmental area influences natural and opiate reward.

Natural reward and drugs of abuse converge on the mesolimbic pathway and activate common mechanism of neural plasticity in the nucleus accumbens. Chronic exposure to opiates induces plasticity in dopaminergic neurons of the ventral tegmental area (VTA), which regulates morphine reward tolerance. Here, we test the hypotheses that mating-induced release of endogenous opioids in the VTA causes morphological changes of VTA dopamine cells in male rats, which in-turn regulate the long-term expression of experience-induced reinforcement of sexual behavior. First, sexual experience decreased VTA dopamine soma size 1 and 7 days, but not 30 days after the last mating session. This effect was blocked with naloxone before each mating session; thus, VTA dopamine cell plasticity was dependent on action of endogenous opioids. In turn, VTA plasticity was associated with altered opiate reward, as sexually experienced males did not form conditioned place preference for 0.5 mg/kg morphine. Next, it was determined whether endogenous opioid action mediates sexual reward and memory in male rats treated with naloxone during mating experience, either systemically or intra-VTA. Naloxone did not prevent the initial experience-induced facilitation of sexual behavior over repeated mating sessions, or conditioned place preference for mating. However, naloxone treatment attenuated the longer-term expression of experience-induced facilitation of sexual behavior and neural activation in mesolimbic areas induced by mating-associated conditioned cues. Together, these data demonstrate that endogenous opioids during mating induce neural plasticity in VTA dopamine neurons that appear critical for morphine reward and long-term memory for natural reward behavior.

Concurrent exposure to methamphetamine and sexual behavior enhances subsequent drug reward and causes compulsive sexual behavior in male rats.

Methamphetamine (Meth) users report having heightened sexual pleasure, numerous sexual partners, and engaging in unprotected sex due to loss of inhibitory control. This compulsive sexual behavior contributes to increased prevalence of sexually transmitted infections, but the neural basis for this is unknown. We previously established a paradigm for compulsive sexual behavior in male rats in which visceral illness induced by lithium chloride was paired with sexual behavior (Davis et al., 2010; Frohmader et al., 2010a). The current study examined the effects of repeated Meth administration on sexual performance, compulsive sexual behavior, and sex or Meth reward. First, results demonstrated that seven daily administrations of 2 mg/kg, but not 1 mg/kg, Meth increased latencies to initiate mating. This impairment was evident 30 min after last Meth administration, but dissipated after 1 or 7 d of subsequent drug abstinence. Repeated 1 mg/kg Meth exposure resulted in compulsive sex-seeking behavior 2 weeks following last Meth administration. This effect was dependent on Meth administration being concurrent with sexual experience and was not observed in sexually experienced animals that received Meth alone. Moreover, concurrent Meth and sexual experience enhanced conditioned place preference (CPP) for Meth, and for concurrent Meth and mating compared with Meth or mating alone. In contrast, CPP for mating alone was decreased. Together, these data indicate that the association between drug use and mating may be required for expression of compulsive sexual behavior and is correlated with increased reward seeking for concurrent Meth exposure and mating.

Effects of methamphetamine on sexual performance and compulsive sex behavior in male rats.

RATIONALE: Methamphetamine (Meth) is a highly addictive psychostimulant associated with enhanced sexual desire, arousal, and sexual pleasure. Moreover, Meth abuse is frequently linked with the practice of sexual risk behavior and increased prevalence of human immunodeficiency virus. Currently, there is a lack of studies investigating the effects of Meth on maladaptive sexual behavior under controlled experimental settings in animal studies. OBJECTIVE: The overall objective of the current study was to examine the effects of Meth on various aspects of male sexual behavior including maladaptive sex-seeking behavior. METHODS: First, a dose-response curve of the effects of Meth (0, 1, 2, and 4 mg/kg; s.c.) on sexual motivation and performance was conducted in sexually naïve and experienced male rats. Next, the effects of Meth (1 mg/kg; s.c.) on inhibition of maladaptive sexual behavior was tested using a sex aversion conditioning paradigm, in which visceral illness induced by lithium chloride (LiCl) was paired with sexual behavior. RESULTS: Meth administration inhibited sexual performance in a dose-dependent matter as evidenced by the decreased percentages of males that mated and increased latencies to initiate sexual behavior when injected with 2 or 4 mg/kg Meth. Moreover, an acute dose of Meth prior to or following sex aversion conditioning resulted in disrupted conditioned inhibition of sexual behavior. CONCLUSIONS: These data suggest that Meth administration in male rats impairs sexual motivation and performance. In addition, low doses of Meth that do not disrupt sexual function may result in maladaptive seeking of sexual behavior.

Mixing pleasures: review of the effects of drugs on sex behavior in humans and animal models.

Drugs of abuse act on the brain circuits mediating motivation and reward associated with natural behaviors. There is ample evidence that drugs of abuse impact male and female sexual behavior. First, the current review discusses the effect of drugs of abuse on sexual motivation and performance in male and female humans. In particular, we discuss the effects of commonly abused drugs including psychostimulants, opiates, marijuana/THC, and alcohol. In general, drug use affects sexual motivation, arousal, and performance and is commonly associated with increased sexual risk behaviors. Second, studies on effects of systemic administration of drugs of abuse on sexual behavior in animals are reviewed. These studies analyze the effects on sexual performance and motivation but do not investigate the effects of drugs on risk-taking behavior, creating a disconnect between human and animal studies. For this reason, we discuss two studies that focus on the effects of alcohol and methamphetamine on inhibition of maladaptive sex-seeking behaviors in rodents. Third, this review discusses potential brain areas where drugs of abuse may be exerting their effect on sexual behavior with a focus on the mesolimbic system as the site of action. Finally, we discuss recent studies that have brought to light that sexual experience in turn can affect drug responsiveness, including a sensitized locomotor response to amphetamine in female and male rodents as well as enhanced drug reward in male rats.