Examining the effectiveness and implementation of patient treatment decision-aid tools for men with localised prostate cancer: A systematic review.

OBJECTIVE: Men diagnosed with localised prostate cancer (LPC) often face a difficult process deciding on a treatment choice that suits their personal preferences. This systematic review examines the impact of patient treatment decision-aids (DAs) on decisional outcomes and treatment choice for men diagnosed with LPC. Our secondary aim was to examine how DAs have been implemented into routine clinical practice. METHODS: A systematic search was conducted up to June 2022 using the following databases: Medline, Embase, PsycINFO, CINAHL, Cochrane, Scopus, and Web of Science. Articles were included if they evaluated the effectiveness of treatment DAs for LPC patients on various decisional outcomes and treatment choice. The Mixed-Method Appraisal Tool was used to assess methodological quality and risk of bias. Data on implementation outcomes were also extracted if reported. RESULTS: Twenty-four articles were included for the analysis (seven non-randomised studies, 16 randomised control trials, and one qualitative study). Results showed DAs have the potential to improve patient knowledge but revealed no effects on decisional regret or preparedness in decision-making. Due to the variability in methodology among studies, results varied widely for treatment choice, decision-making involvement, decisional conflict, and treatment decision satisfaction. At least one implementation outcome was reported in 11 of the included studies, with the most commonly assessed outcomes being acceptability and appropriateness. CONCLUSIONS: While DAs appear to improve knowledge, further qualitative evaluations and standardised assessments are needed to better understand men's experiences using DAs and to determine advantages and optimal ways to implement DAs into the treatment decision-making pathway.

Psychological distress, understanding of cancer and illness uncertainty in patients with Cancer of Unknown Primary.

OBJECTIVE: Patients diagnosed with Cancer of Unknown Primary (CUP) experience high levels of psychological distress and report poor understanding of their cancer. We aimed to investigate: (1) if CUP patients with poorer understanding of their cancer diagnosis and testing experience more symptoms of psychological distress than those with better understanding; (2) if the relationship between patients' understanding of their cancer and psychological distress is mediated by illness uncertainty; and (3) explore whether patients' degree of understanding of their cancer can be predicted by clinical and socio-demographic factors. METHODS: 209 CUP patients completed a questionnaire measuring anxiety, depression, illness uncertainty, fatigue, pain, sleep and understanding of their cancer. Using an apriori theoretical framework, we employed structural equation modelling to investigate predictors of patient's understanding of their cancer and psychological distress and the relationships between understanding, illness uncertainty and distress. RESULTS: The structural equation model displayed good fit indices and supported the hypothesised relationship of patient's understanding of their cancer and the extent of psychological distress, which was mediated via illness uncertainty. Physical symptoms were positively associated with psychological distress and illness uncertainty. Younger age was predictive of lower patient's understanding of their cancer and higher levels of psychological distress. CONCLUSIONS: Patients with CUP, particularly those who are younger and experiencing more physical symptoms, report higher levels of psychological distress and may require additional mental health support. Our findings highlight a need to improve CUP patient's understanding about their illness, which could help reduce their illness uncertainty and alleviate psychological distress.

Understanding and information needs of cancer patients regarding treatment-focused genomic testing: A systematic review.

OBJECTIVE: To systematically review literature exploring experiences of cancer patients regarding their understanding of treatment-focused genomic testing as well as their information needs and related themes. METHODS: Six databases were searched for the original studies published in English language that explored patients' understanding of the information related to the genomic testing and its implications for treatment of cancer. The Mixed-Method Assessement Tool was used to examine the methodological quality of selected articles. RESULTS: There were 14 studies (5 qualitative and 9 quantitative) that met inclusion and exclusion criteria. The majority of studies revealed that a considerable proportion of cancer patients lacked good undertstanding of treatment-focused genomic testing and wanted to be better informed. Some of the factors associated with poor knowledge about genomic testing were low education, older age, low income, and unemployment. The majority of people with cancer preferred face-to-face communication with their oncologists to discuss and ask questions about genomic testing and treatment. Most also wanted to receive simple, easy to understand written information about treatment-focused genomic testing. CONCLUSIONS: Genomic testing and its implications for treatment emerge as an important aspect of health care across different types of cancer. The evidence indicates that cancer patients want to understand and be well informed about treatment-focused genomic testing in order to be part of decision-making process. Further studies addressing ways to improve cancer patients' understanding and knowledge of genomic testing are needed.

Adolescent exposure to fluoxetine impairs serial pattern learning in the serial multiple choice (SMC) task in adult rats.

The effects of chronic adolescent fluoxetine (FLX, Prozac®) exposure on adult cognition are largely unknown. We used a serial multiple choice (SMC) task to characterize the effects of adolescent FLX exposure on rat serial pattern learning in adulthood. Male rats were exposed to either 1.0, 2.0, or 4.0 mg/kg/day FLX for five consecutive days each week for five weeks during adolescence, followed by a 35-day drug-free period. As adults, the rats were trained in a task that required them to learn a highly structured sequential pattern of responses in an octagonal chamber for water reinforcement. In a transfer phase, the terminal element of the pattern was replaced by a violation element that was inconsistent with previously learned pattern structure. Results indicated that adolescent FLX exposure caused differential learning deficits for different types of elements in the serial pattern. Adolescent exposure to 1.0 or 4.0 mg/kg/day FLX, but not 2.0 mg/kg/day FLX, impaired chunk-boundary element learning, which is known to be mediated by stimulus-response (S-R) learning. All three doses of FLX impaired violation element learning, which is known to be mediated by multiple-cue learning. FLX did not impair within-chunk element learning, which is known to be mediated by rule-learning mechanisms. The results indicate that adolescent FLX exposure produced multiple cognitive impairments that were detectable in adulthood long after drug exposure ended.

Serial pattern retention in male and female rats.

Serial pattern learning is a model paradigm for studying parallel-processing in complex learning in rats. The current experiment extends the paradigm to the study of sequential memory by examining forgetting curves for the component element types that make up a serial pattern. Adult male and female rats were trained in a serial multiple choice (SMC) task in which rats learned a serial pattern of nose-poke responses in a circular array of 8 receptacles mounted on the walls of an octagonal operant chamber. The pattern was 123-234-345-456-567-678-781-818, where digits represent the clockwise positions of successive correct receptacles. Previous work has shown that chunk-boundary elements (the first element of each 3-element chunk), within-chunk elements (the second and third elements in all but the last chunk), and the violation element (the last element of the pattern) are learned via different cognitive mechanisms. After each rat was trained to an 85% correct performance criterion on the violation element, we then assessed serial pattern retention at 24-h, 2-week, and 4-week retention intervals. For chunk-boundary and within-chunk elements, forgetting was observed only at the 4-week retention interval. Sex differences were observed; females performed better than males on within-chunk elements at 24-h and 4-week retention intervals. For the violation element, significant forgetting was observed earlier at the 2-week retention interval as well as at the 4-week retention interval. Thus, pattern elements that were learned slower were forgotten faster. The experiment provides a proof of concept for evaluating forgetting curves separately for the multiple memory systems rats appear to employ concurrently in this paradigm, a method that may prove useful in characterizing the impact of relevant neurobiological manipulations on forgetting in multiple sequential memory systems.

Psychological distress, role, and identity changes in mothers following a diagnosis of cancer: A systematic review.

OBJECTIVE: To systematically review findings of the impact of cancer diagnosis and treatment on mothers' psychological well-being, roles, and identity and to explore the psychosocial factors that contribute to mothers' psychological well-being. METHODS: Six databases were searched for research articles and theses exploring the association between the impact of cancer diagnosis and treatment on mothers' psychological well-being, identity, and role, and the psychosocial factors contributing to mothers' psychological distress regardless of their cancer type and stage. The Mixed-Method Appraisal Bias Tool was used to assess the selected studies' methodological quality. RESULTS: A total of 30 qualitative, quantitative, and mixed-method studies were deemed eligible for inclusion. Most studies reported that mothers experienced significant psychological distress, changes to or loss of parenting efficacy, maternal identity, and role. Psychosocial factors that contributed to mothers' distress included mothers' young age, presence of metastases, lower parenting efficacy, fear of cancer recurrence, higher illness intrusiveness, and lack of appropriate support. Four main themes emerged from the qualitative studies: psychological impact of cancer on mothers, changes in maternal identity and role, relationship changes and concerns for their children, and meaning-making in cancer experience. CONCLUSIONS: Changes in mothers' psychological well-being, role, and identity occurred across cancer diagnoses, treatment, and recovery trajectories. The evidence suggests that mothers may benefit from continued and tailored psychosocial support to cope with these challenges, even after treatment is completed. Further studies with improved methodological quality are needed to explore these issues in depth.

Self-compassion and parenting efficacy among mothers who are breast cancer survivors: Implications for psychological distress.

Mothers who are breast cancer survivors may experience psychological distress in relation to diminished parenting efficacy. Self-compassion may protect mothers from psychological distress, yet little is known about self-compassion in this population. The extent to which self-warmth (self-kindness, mindfulness and sense of common humanity) and self-coldness (self-judgement, isolation and over-identification) dimensions of self-compassion moderate parenting efficacy in predicting depression, anxiety and stress was examined in a sample of 95 mothers who were breast cancer survivors. Independently, poorer parenting efficacy was associated with more depression and stress symptoms. Within regression models, self-coldness was a direct predictor of depression, anxiety and stress, while self-warmth moderated the relationship between parenting efficacy and stress. Self-warmth presents as a potential protective factor for stress associated with poor parenting efficacy, while self-coldness is a potential direct risk factor for psychological distress. Mothers who are breast cancer survivors may benefit from self-compassion focused psychosocial interventions.

Shame and Emotion Dysregulation as Pathways to Posttraumatic Stress Symptoms Among Women With a History of Interpersonal Trauma.

Women who have survived interpersonal trauma are at elevated risk of developing posttraumatic stress disorder (PTSD), and potentially modifiable factors that may be targeted in treatment warrant further investigation. This study examined a pathway from interpersonal trauma to PTSD symptoms via emotion dysregulation and shame in a large non-clinical sample of women. The sample comprised 380 women, aged 18 to 59 years (M = 31.70, standard deviation = 10.06), all of whom had a history of interpersonal trauma. Participants completed the Experience of Shame Scale, the Difficulties in Emotion Regulation Scale-Short Form, and the Life Events Checklist for DSM-5. A serial and parallel process model with interpersonal trauma as a predictor of PTSD symptoms, emotional dysregulation and facets of shame as intermediary variables, was analyzed using Statistical Package for Social Sciences Statistics PROCESS Model 81with bias-corrected bootstrap tests of indirect effects. Non-interpersonal trauma was included as a covariate. Interpersonal trauma, emotion dysregulation, and characterological and bodily shame were significantly and directly associated with PTSD symptoms, together explaining 59% of the variation in PTSD symptoms. While emotion dysregulation was associated with behavioral shame, interpersonal trauma was not associated with behavioral shame, nor was behavioral shame associated with PTSD symptoms. Tests of indirect effects supported a pathway from interpersonal trauma to PTSD symptoms via emotion dysregulation and characterological and bodily shame. These findings suggest interventions that are particularly effective at reducing emotion dysregulation and characterological and bodily shame, such as compassion and acceptance-based approaches, may complement evidence-based PTSD interventions when working with women who have survived interpersonal trauma.

The effects of gonadal hormones on heroin Self-Administration in male gonadectomized rats.

RATIONALE: Previous studies have shown that gonadal hormones influence opioid self-administration in female rodents, but very few studies have examined these effects in male rodents. OBJECTIVES: The purpose of this study was to examine the effects of chronic hormone treatment on intravenous heroin self-administration in gonadectomized male rats using both physiological and supraphysiological doses of testosterone, estradiol, or progesterone. METHODS: Gonadectomized male rats were surgically implanted with intravenous catheters and trained to self-administer heroin on a fixed ratio (FR1) schedule of reinforcement. Using a between-subjects design, rats were treated daily with testosterone (0.175 or 1.75 mg, sc), estradiol (0.0005 or 0.005 mg, sc), progesterone, (0.0125 or 0.125 mg, sc), or their vehicles. After 14 days of chronic treatment, a dose-effect curve was determined for heroin (0.0003-0.03 mg/kg/infusion) over the course of one week. RESULTS: Neither testosterone nor estradiol altered responding maintained by heroin. In contrast, the high dose of progesterone (0.125 mg) reduced responding maintained by all doses of heroin to saline-control levels. This dose of progesterone did not reduce responding maintained by food on a progressive ratio schedule in either food-restricted or food-sated rats. CONCLUSIONS: These data indicate that exogenous progesterone or a pharmacologically active metabolite selectively decreases heroin intake in male rodents, which may have therapeutic implications for men with opioid use disorder.

Trajectories of distress in women with gynaecological cancer treated with curative-intent radiotherapy.

OBJECTIVE: The aims of this study were to investigate trajectories of anxiety and depression symptoms among gynaecological cancer (GC) patients having curative-intent radiotherapy (RT) treatment and identify which patient characteristics predict anxiety and depression trajectories. METHODS AND MEASURES: Latent profile analysis (LPA) was used to identify unique trajectories of anxiety and depression symptoms, spanning prior to the start of RT until 12-month post-RT, among 151 GC patients in the PeNTAGOn randomized control trial. Demographic and clinical characteristics were assessed at baseline, and anxiety and depression symptoms were assessed five times over 12 months. A bias-adjusted 3-step maximum likelihood approach was used to identify demographic and clinical predictors of trajectory profiles. RESULTS: Four latent profiles each were identified for anxiety and depression trajectories. Most patients had minimal to mild levels of anxiety or depression that remained steady or declined over 12 months following treatment. A minority of patients were in profiles that exhibited clinically significant distress; either 'High fluctuating' anxiety or 'Mild-moderate fluctuating' depression. Anxiety and depression profiles were predicted by clinical and demographic factors, such as age, living arrangements, RT type, cancer stage, physical symptom distress and use of support services. CONCLUSIONS: Psychological care of patients in the higher distress trajectories is paramount and, importantly, they could be identified prior to treatment based on the factors identified. Review for at least a month post-RT is warranted.

A Qualitative Study of Men's Experiences Using Navigate: A Localized Prostate Cancer Treatment Decision Aid.

Background. Men diagnosed with localized prostate cancer (LPC) often face a dilemma in choosing between available treatment options that have similar survival rates but for which the perceived advantages and disadvantages of each treatment differ. The Navigate decision aid was created to assist Australian men with LPC in making informed decisions about treatment that align with their personal values and preferences. Navigate presents current, unbiased information, including an interactive values clarification exercise. Objective. This study was a qualitative investigation of men's treatment decision making for LPC, and their experiences using the Navigate Web site, to identify areas for improvement and inform implementation. Methods. Semi-structured interviews were conducted with 20 men diagnosed with LPC who completed the intervention arm of the Navigate randomized controlled trial. Interview transcripts were thematically analyzed. Results: Five main themes emerged: 1) diagnosis experiences varied, although men were strongly influenced by their clinician to make an early initial treatment decision; 2) men sought resources and support they trusted; 3) men valued Navigate's multiformatted content and design; 4) men suggested more content was needed on a) the diagnosis journey and b) new treatment updates; and 5) men identified design flaws in the values clarification exercise on Navigate but appreciated the tool being available. Conclusions. Specialist authority influenced men to make an early treatment decision. However, Navigate was helpful in supporting men's ongoing treatment decision making, particularly men on active surveillance who may face further treatment decisions if their cancer progresses. To gain trust and improve engagement from Navigate users, credentials and sources of information need to be prominent. Trustworthiness, timing of access, and the clinician's role in empowering men to use available decision aids are crucial elements to be considered when implementing Navigate in clinical settings. Highlights: The Navigate decision aid Web site was created to help Australian men diagnosed with localized prostate cancer (LPC) make an informed decision about their treatment.Navigate was helpful in supporting men's ongoing treatment decision making for LPC.Men's treatment decision making for LPC was greatly influenced by perceived authority and trust in their clinician.Trustworthiness, timing of access, and the clinician's role in empowering men to use available decision aids are crucial.

Fear of cancer recurrence as a pathway from fatigue to psychological distress in mothers who are breast cancer survivors.

Fatigue is prevalent and pervasive among breast cancer survivors. Mothers are particularly susceptible to fatigue due to the ongoing demands of their caring role. While fatigue has been associated with psychological distress in prior research, the pathway by which fatigue translates into psychological distress is unclear. Given the theoretical and empirical links between fatigue, fear of cancer recurrence (FCR) and psychological distress, the role of FCR in mediating the relationship between fatigue and psychological distress in mothers who are breast cancer survivors was investigated. Ninety-two mothers who were breast cancer survivors completed the Depression, Anxiety and Stress Scale, PROMIS-Cancer Fatigue Short Form and Concerns About Cancer Recurrence scale in an online survey. Mediation analysis via PROCESS was used to examine whether fatigue predicted depression, anxiety or stress through FCR. Fear of cancer recurrence mediated the relationships between fatigue and anxiety and fatigue and stress, while fatigue directly predicted depression. This study highlights FCR as a potential pathway to anxiety and stress in response to ongoing fatigue, and as a mechanism of action to reduce psychological distress among mothers who are breast cancer survivors. Future research examining this pathway from fatigue to psychological distress should also explore the nature of mothers' fears about their cancer recurring.

Demand and cross-price elasticity of cocaine and social contact in a free-operant procedure of nonexclusive choice.

Research examining the social determinants of addiction has advanced significantly with the recent development of preclinical models of drug use and the social environment. These models reveal that drug use and social contact compete with one another for behavioral expression in discrete-trial choice procedures using concurrent schedules of reinforcement. The purpose of this study was to determine how concurrent access to cocaine and a social partner influences the demand for each alternative under free-operant conditions in which responding maintained by each reinforcer is independent and nonexclusive of the other. To this end, male rats were trained under a free-operant, concurrent schedule of reinforcement in which responding maintained by cocaine and access to a social partner operated independently of one another. Measures of economic demand (e.g., intensity, Omax, cross-price elasticity) were determined by manipulating the response requirement (i.e., fixed ratio value) across sessions. Tests were conducted in which the social partner was either treated or not treated with cocaine to determine whether the intoxication state of the partner influenced demand. The principal findings of this study are (1) demand for a cocaine-treated partner is greater than demand for a cocaine-free partner, (2) demand for cocaine is greater in the presence of a cocaine-treated partner than a cocaine-free partner, and (3) concurrent access to cocaine decreases demand for social contact. Notably, measures of cross-price elasticity indicated that social contact is a robust economic substitute for cocaine.

Sex differences in opioid receptor mediated effects: Role of androgens.

An abundance of data indicates there are sex differences in endogenous opioid peptides and opioid receptors, leading to functional differences in sensitivity to opioid receptor mediated behaviors between males and females. Many of these sex differences are mediated by the effects of gonadal hormones on the endogenous opioid system. Whereas much research has examined the role of ovarian hormones on opioid receptor mediated endpoints, comparatively less research has examined the role of androgens. This review describes what is currently known regarding the influence of androgens on opioid receptor mediated endpoints and how androgens may contribute to sex differences in these effects. The review also addresses the clinical implications of androgenic modulation of opioid receptor mediated behaviors and suggests future lines of research for preclinical and clinical investigators. We conclude that further investigation into androgenic modulation of opioid receptor mediated effects may lead to new options for addressing conditions such as chronic pain and substance use disorders.

Child maltreatment and post-traumatic growth: Implications for the well-being of young adults.

BACKGROUND: Little is known about the relationship between childhood maltreatment and well-being in young adults, including the role of post-traumatic growth (PTG) in promoting better outcomes for young adults who have a history of childhood maltreatment (HCM). OBJECTIVE: To examine the relationship between child maltreatment and well-being among young adults, by considering the perpetrator and the extent of the maltreatment, as well as PTG among young adults with a HCM. PARTICIPANTS AND SETTING: The sample comprised 537 young adults (aged 18-25; M = 21.09 years, SD = 2.36) from across Australia, with 182 young adults in the sample forming the cohort with a HCM. METHOD: Participants' current well-being, the extent of maltreatment by their mother, father and other adults experienced as a child (<18 years), and PTG was collected using an online survey. Tests of group differences and multiple regression were conducted to analyse the relationships between child maltreatment, PTG, and current well-being. RESULTS: Maltreatment by one's mother or father predicted poorer current well-being, but not maltreatment by another adult. Young adults who identified as having a HCM had poorer well-being than those who did not. Within the cohort of those with a HCM, greater PTG predicted greater well-being, and also mitigated the negative relationship between child maltreatment by one's father and well-being. CONCLUSION: Findings indicate that both the extent of child maltreatment and the relationship to the perpetrator have implications for well-being among young adults. PTG appeared to play a protective role, highlighting the potential therapeutic benefit of fostering PTG to improve well-being among young adults with a HCM.

The effects of artificially induced proestrus on heroin intake: A critical role for estradiol.

Heroin intake decreases markedly during proestrus in normally cycling female rats; however, it is not known whether estradiol, progesterone, or both hormones are responsible for these decreases in heroin intake. The purpose of the present study was to examine the roles of estradiol and progesterone in heroin intake by artificially inducing a proestrus state in ovariectomized rats. To this end, ovariectomized female rats were implanted with intravenous catheters and trained to self-administer heroin (0.0075 mg/kg/infusion) on a fixed ratio (FR1) schedule of reinforcement. After 1 week of training, rats were tested at weekly intervals with estradiol (0.005 mg, sc) or vehicle 22 hr before a test session and progesterone (0.125 mg, sc) or vehicle 0.5 hr before a test session to artificially mimic the naturally occurring hormone concentrations characteristic of late proestrus. Administration of estradiol 22 hr prior to testing and progesterone 0.5 hr prior to testing significantly reduced heroin intake relative to the previous training day and vehicle control. It is interesting that this same effect was observed when only estradiol, but not progesterone, was administered. These data suggest that estradiol but not progesterone is responsible for the proestrus-induced decreases in heroin intake previously reported in normally cycling female rats. These findings differ from those reported previously with stimulants and suggest that estrogen-based pharmacotherapies may be of value to women with opioid use disorder. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The Effects of Drugs on Behavior Maintained by Social Contact: Role of Monoamines in Social Reinforcement.

Drug use is highly concordant among members of adolescent and young adult peer groups. One potential explanation for this observation is that drugs may increase the reinforcing effects of social contact, leading to greater motivation to establish and maintain contact with other members of the peer group. Several classes of drugs, particularly drugs that increase synaptic dopamine, increase the reinforcing effects of contextual stimuli, but the extent to which these drugs enhance the reinforcing effects of social contact is not known. The purpose of this study was to determine the extent to which drugs that increase synaptic dopamine, norepinephrine, and serotonin enhance the positive reinforcing effects of social contact. To this end, male and female Long-Evans rats were pretreated with acute doses of the selective dopamine reuptake inhibitor, WIN-35,428, the selective norepinephrine reuptake inhibitor, atomoxetine, the selective serotonin reuptake inhibitor, fluoxetine, the non-selective monoamine reuptake inhibitor, cocaine, and the non-selective monoamine releasers d-amphetamine and (±)-MDMA. Ten minutes later, the positive reinforcing effects of 30-s access to a same-sex social partner was examined on a progressive ratio schedule of reinforcement. To determine whether the reinforcement-altering effects of these drugs were specific to the social stimulus, the reinforcing effects of a non-social stimulus (30-s access to an athletic sock of similar size and coloring as another rat) was determined in control subjects. WIN-35,428, d-amphetamine, and cocaine, but not atomoxetine, fluoxetine, or MDMA, dose-dependently increased breakpoints maintained by a social partner under conditions in which responding maintained by a non-social stimulus was not affected. These data indicate that increases in extracellular dopamine, but not extracellular norepinephrine or serotonin, increases the positive reinforcing effects of social contact in both male and female rats. These data also provide support for the hypothesis that some drugs with high abuse liability increase the motivation to establish and maintain contact with social peers.

Social Contact Reinforces Cocaine Self-Administration in Young Adult Male Rats: The Role of Social Reinforcement in Vulnerability to Drug Use.

Drug-using peers are recognized as a leading factor influencing drug use among adolescents and young adults. One mechanism by which peers influence drug use is by providing social reinforcement for using drugs. Social reinforcement may be provided in multiple ways, including by making social contact contingent on drug use (i.e., an individual must use drugs to gain/maintain access to a peer). The purpose of this study was to develop a preclinical model in which intravenous cocaine self-administration was positively reinforced by access to a social partner. Young adult male rats were trained to self-administer cocaine in operant conditioning chambers with a guillotine door that could be opened to an adjacent compartment housing either a social partner or a non-social stimulus. Once cocaine self-administration was established, the guillotine door was activated, and cocaine intake was reinforced by brief access to either a social (age- and sex-matched peer) or non-social (black-and-white athletic sock) stimulus. Contingent access to a social partner rapidly increased cocaine self-administration. Total cocaine intake was 2- to 3-fold greater in rats assigned to the social versus non-social condition across a 100-fold dose range. Cocaine intake rapidly increased when rats in the original non-social group were later provided with social partners, whereas cocaine intake resisted change and remained elevated when rats in the original social group had their partners removed. These data indicate that contingent access to a social partner increases drug intake and suggest that social reinforcement may represent a vulnerability factor that is particularly resistant to psychosocial interventions.

The effects of chronic estradiol treatment on opioid self-administration in intact female rats.

Heroin intake decreases significantly during proestrus in normally cycling female rats, and this effect is mediated by endogenous estradiol but not endogenous progesterone. The purpose of this study was to determine whether chronic administration of exogenous estradiol decreases intake of the semi-synthetic opioid, heroin, and the fully synthetic opioid, remifentanil, in intact female rats. Normally cycling female rats were implanted with intravenous catheters and trained to self-administer heroin on a fixed ratio (FR1) schedule of reinforcement. Rats were treated chronically with daily administration of either a low dose of estradiol (0.5 mcg, sc), a high dose of estradiol (5.0 mcg, sc), or vehicle (peanut oil, sc). After two weeks of heroin self-administration training, dose-effect curves were determined for both heroin and remifentanil. Chronic administration of estradiol non-significantly decreased heroin intake and significantly decreased remifentanil intake. Estradiol-induced decreases in remifentanil intake were dose-dependent, characterized by large effect sizes, and greatest in rats treated with the high dose of estradiol. These data indicate that chronic estradiol administration decreases opioid intake in intact female rats with medium to large effect sizes across opioids. These findings suggest that estrogen-based pharmacotherapies may represent a novel treatment approach for women with opioid use disorder.

Lack of evidence for positive reinforcing and prosocial effects of MDMA in pair-housed male and female rats.

3,4-Methylenedioxymethamphetamine (MDMA) is classified as an entactogen, producing feelings of emotional openness and relatedness. One unique feature of MDMA is that people tend to selectively take this drug in social and/or intimate situations. Although MDMA is recognized as having abuse liability, preclinical studies report that it has weak reinforcing effects in animals. The objective of this study was to characterize the positive reinforcing and prosocial effects of MDMA in a translational model of the social environment in which two rats have simultaneous and contingent access to MDMA in close physical proximity. To this end, MDMA self-administration was examined on both fixed and progressive ratio schedules of reinforcement in six groups of rats: (1) isolated males, (2) isolated females, (3) male-male dyads, (4) female-female dyads, (5) male-female dyads, and (6) female-male dyads. For pair-housed rats, data from both rats were analyzed. Next, social preferences were examined in a partner preference test. MDMA failed to produce positive reinforcing effects under all conditions examined. Across a 30-fold dose range (0.01-1.0 mg/kg/infusion), MDMA did not maintain higher responding than saline on both schedules of reinforcement and in all groups tested. In partner preference tests, a history of shared exposure to MDMA did not establish a social preference, and acute administration of MDMA failed to establish a preference for another MDMA-treated rat. These data suggest that social contact does not increase the positive reinforcing effects of MDMA in rats, and that neither contingent nor noncontingent MDMA administration establishes a social preference in rats.