Fatigability of the external anal sphincter muscles using a novel strength training resistance exercise device.

Exercises involving pelvic floor muscles including repetitive voluntary contractions of external anal sphincter (EAS) musculature have been used to improve fecal incontinence. Muscle fatigue is a prerequisite for successful strength training. However, muscle fatigue induced by these exercises has not been systematically studied. We aimed to assess the fatigability of EAS muscles during various exercise methods. Twelve nulliparous (21 ± 2.7 yr) women were studied. We evaluated fatigue during 40 repetitive 3-s contractions and 30-s long squeeze contractions both with and without an intra-anal compressible resistant load. The sequence of exercises was randomized. This load was provided by the continence muscles Resistance Exerciser Device. Anal canal pressures were recorded by high-resolution manometry. Exercise against a resistive load showed significant decrease in anal contractile integral (CI) and maximum squeeze pressure during repetitive short squeeze contractions compared with exercise without a load. Linear regression analysis showed a significant negative correlation between anal CI and successive contraction against load, suggesting "fatigue." Similar findings were observed for maximum squeeze pressure (slope with load = -4.2, P = 0.0003, vs. without load = -0.9, P = 0.3). Long squeeze contraction against a load was also more susceptible to fatigue than without a load (P < 0.0001). In conclusion, repetitive contractions against a compressible load induce fatigue and thus have the potential to strengthen the anal sphincter contractile function than contractions without a load. Fatigue rate in long squeeze contraction exercises with a load is significantly faster than that without a load, also indicating greater effectiveness in inducing muscle fatigue.NEW & NOTEWORTHY Fecal incontinence is a distressing disorder with a mainstay of treatment being pelvic floor muscle exercises. However, none of these exercises has proven occurrence of fatigability, which is an important prerequisite for successful muscle strengthening in rehabilitative exercises. In this study, we proved that we can fatigue the external anal sphincter muscles more efficiently by providing a resistive load during anal repetitive short squeeze contractions and long squeeze contraction exercise.

Investigating Practical Impacts of Using Single-Antenna and Dual-Antenna GNSS/INS Sensors in UAS-Lidar Applications.

Data collected from a moving lidar sensor can produce an accurate digital representation of the physical environment that is scanned, provided the time-dependent positions and orientations of the lidar sensor can be determined. The most widely used approach to determining these positions and orientations is to collect data with a GNSS/INS sensor. The use of dual-antenna GNSS/INS sensors within commercial UAS-lidar systems is uncommon due to the higher cost and more complex installation of the GNSS antennas. This study investigates the impacts of using a single-antenna and dual-antenna GNSS/INS MEMS-based sensor on the positional precision of a UAS-lidar generated point cloud, with an emphasis on the different heading determination techniques employed by each type of GNSS/INS sensor. Specifically, the impacts that sensor velocity and acceleration (single-antenna), and a GNSS compass (dual-antenna) have on heading precision are investigated. Results indicate that at the slower flying speeds often used by UAS (≤5 m/s), a dual-antenna GNSS/INS sensor can improve heading precision by up to a factor of five relative to a single-antenna GNSS/INS sensor, and that a point of diminishing returns for the improvement of heading precision exists at a flying speed of approximately 15 m/s for single-antenna GNSS/INS sensors. Additionally, a simple estimator for the expected heading precision of a single-antenna GNSS/INS sensor based on flying speed is presented. Utilizing UAS-lidar mapping systems with dual-antenna GNSS/INS sensors provides reliable, robust, and higher precision heading estimates, resulting in point clouds with higher accuracy and precision.

Critical Care Basic Ultrasound Learning Goals for American Anesthesiology Critical Care Trainees: Recommendations from an Expert Group.

OBJECTIVE: In this review, we define learning goals and recommend competencies concerning focused basic critical care ultrasound (CCUS) for critical care specialists in training. DESIGN: The narrative review is, and the recommendations contained herein are, sponsored by the Society of Critical Care Anesthesiologists. Our recommendations are based on a structured literature review by an expert panel of anesthesiology intensivists and cardiologists with formal training in ultrasound. Published descriptions of learning and training routines from anesthesia-critical care and other specialties were identified and considered. Sections were written by groups with special expertise, with dissent included in the text. RESULTS: Learning goals and objectives were identified for achieving competence in the use of CCUS at a specialist level (critical care fellowship training) for diagnosis and monitoring of vital organ dysfunction in the critical care environment. The ultrasound examination was divided into vascular, abdominal, thoracic, and cardiac components. For each component, learning goals and specific skills were presented. Suggestions for teaching and training methods were described. DISCUSSION: Immediate bedside availability of ultrasound resources can dramatically improve the ability of critical care physicians to care for critically ill patients. Anesthesia--critical care medicine training should have definitive expectations and performance standards for basic CCUS interpretation by anesthesiology--critical care specialists. The learning goals in this review reflect current trends in the multispecialty critical care environment where ultrasound-based diagnostic strategies are already frequently applied. These competencies should be formally taught as part of an established anesthesiology-critical care medicine graduate medical education programs.

Chemogenetic activation of corticotropin-releasing factor-expressing neurons in the anterior bed nucleus of the stria terminalis reduces effortful motivation behaviors.

Corticotropin-releasing factor (CRF) in the anterior bed nucleus of the stria terminalis (aBNST) is associated with chronic stress and avoidance behavior. However, CRF + BNST neurons project to reward- and motivation-related brain regions, suggesting a potential role in motivated behavior. We used chemogenetics to selectively activate CRF+ aBNST neurons in male and female CRF-ires-Cre mice during an effort-related choice task and a concurrent choice task. In both tasks, mice were given the option either to exert effort for high value rewards or to choose freely available low value rewards. Acute chemogenetic activation of CRF+ aBNST neurons reduced barrier climbing for a high value reward in the effort-related choice task in both males and females. Furthermore, acute chemogenetic activation of CRF+ aBNST neurons also reduced effortful lever pressing in high-performing males in the concurrent choice task. These data suggest a novel role for CRF+ aBNST neurons in effort-based decision and motivation behaviors.

Influence of Peptoid Sequence on the Mechanisms and Kinetics of 2D Assembly.

Two-dimensional (2D) materials have attracted intense interest due to their potential for applications in fields ranging from chemical sensing to catalysis, energy storage, and biomedicine. Recently, peptoids, a class of biomimetic sequence-defined polymers, have been found to self-assemble into 2D crystalline sheets that exhibit unusual properties, such as high chemical stability and the ability to self-repair. The structure of a peptoid is close to that of a peptide except that the side chains are appended to the amide nitrogen rather than the α carbon. In this study, we investigated the effect of peptoid sequence on the mechanism and kinetics of 2D assembly on mica surfaces using in situ AFM and time-resolved X-ray scattering. We explored three distinct peptoid sequences that are amphiphilic in nature with hydrophobic and hydrophilic blocks and are known to self-assemble into 2D sheets. The results show that their assembly on mica starts with deposition of aggregates that spread to establish 2D islands, which then grow by attachment of peptoids, either monomers or unresolvable small oligomers, following well-known laws of crystal step advancement. Extraction of the solubility and kinetic coefficient from the dependence of the growth rate on peptoid concentration reveals striking differences between the sequences. The sequence with the slowest growth rate in bulk and with the highest solubility shows almost no detachment; i.e., once a growth unit attaches to the island edge, there is almost no probability of detaching. Furthermore, a peptoid sequence with a hydrophobic tail conjugated to the final carboxyl residue in the hydrophilic block has enhanced hydrophobic interactions and exhibits rapid assembly both in the bulk and on mica. These assembly outcomes suggest that, while the π-π interactions between adjacent hydrophobic blocks play a major role in peptoid assembly, sequence details, particularly the location of charged groups, as well as interaction with the underlying substrate can significantly alter the thermodynamic stability and assembly kinetics.

Molecular analysis of primary and metastatic sites in patients with renal cell carcinoma.

BACKGROUNDMetastases are the hallmark of lethal cancer, though underlying mechanisms that drive metastatic spread to specific organs remain poorly understood. Renal cell carcinoma (RCC) is known to have distinct sites of metastases, with lung, bone, liver, and lymph nodes being more common than brain, gastrointestinal tract, and endocrine glands. Previous studies have shown varying clinical behavior and prognosis associated with the site of metastatic spread; however, little is known about the molecular underpinnings that contribute to the differential outcomes observed by the site of metastasis.METHODSWe analyzed primary renal tumors and tumors derived from metastatic sites to comprehensively characterize genomic and transcriptomic features of tumor cells as well as to evaluate the tumor microenvironment at both sites.RESULTSWe included a total of 657 tumor samples (340 from the primary site [kidney] and 317 from various sites of metastasis). We show distinct genomic alterations, transcriptomic signatures, and immune and stromal tumor microenvironments across metastatic sites in a large cohort of patients with RCC.CONCLUSIONWe demonstrate significant heterogeneity among primary tumors and metastatic sites and elucidate the complex interplay between tumor cells and the extrinsic tumor microenvironment that is vital for developing effective anticancer therapies.

The Association between Diet and Sleep Quality among Spanish University Students.

While it has long been recognized that diet is a leading behavioral risk factor for human health, recent scientific findings have also suggested that diet and sleep quality may be connected. The purpose of the present study is to evaluate the association between diet and sleep quality among a group of Spanish university students. To do so, a cross-sectional study of 868 students was carried out. Sleep quality was assessed using the Spanish version of the Pittsburgh Sleep Quality Index (PSQI), while diet was assessed using the Spanish Healthy Eating Index (SHEI). The study revealed a noteworthy rate of bad sleepers (51.6%) and students whose diet needed modifications (82.2%). Unhealthy eaters were more likely to have poor sleep quality (aOR = 4.20; CI 95%: 2.07-8.52). The unbalanced intake of vegetables (aOR = 1.63; CI 95%: 1.14-2.34), fruits (aOR = 4.08; CI 95%: 2.90-5.74), dairy products (aOR = 1.96; CI 95%: 1.41-2.72), lean meats (aOR = 1.82; CI 95%: 1.19-2.78), legumes (aOR = 1.43; CI 95%: 1.00-2.02), sweets (aOR = 1.60; CI 95%: 1.13-2.25) and sugary soft drinks (aOR = 1.46; CI 95%: 1.07-1.99) was associated with lower sleep quality.

Cdk5 promotes synaptogenesis by regulating the subcellular distribution of the MAGUK family member CASK.

Synaptogenesis is a highly regulated process that underlies formation of neural circuitry. Considerable work has demonstrated the capability of some adhesion molecules, such as SynCAM and Neurexins/Neuroligins, to induce synapse formation in vitro. Furthermore, Cdk5 gain of function results in an increased number of synapses in vivo. To gain a better understanding of how Cdk5 might promote synaptogenesis, we investigated potential crosstalk between Cdk5 and the cascade of events mediated by synapse-inducing proteins. One protein recruited to developing terminals by SynCAM and Neurexins/Neuroligins is the MAGUK family member CASK. We found that Cdk5 phosphorylates and regulates CASK distribution to membranes. In the absence of Cdk5-dependent phosphorylation, CASK is not recruited to developing synapses and thus fails to interact with essential presynaptic components. Functional consequences include alterations in calcium influx. Mechanistically, Cdk5 regulates the interaction between CASK and liprin-alpha. These results provide a molecular explanation of how Cdk5 can promote synaptogenesis.

Chronic non-discriminatory social defeat stress reduces effort-related motivated behaviors in male and female mice.

Reward and motivation deficits are prominent symptoms in many mood disorders, including depression. Similar reward and effort-related choice behavioral tasks can be used to study aspects of motivation in both rodents and humans. Chronic stress can precipitate mood disorders in humans and maladaptive reward and motivation behaviors in male rodents. However, while depression is more prevalent in women, there is relatively little known about whether chronic stress elicits maladaptive behaviors in female rodents in effort-related motivated tasks and whether there are any behavioral sex differences. Chronic nondiscriminatory social defeat stress (CNSDS) is a variation of chronic social defeat stress that is effective in both male and female mice. We hypothesized that CNSDS would reduce effort-related motivated and reward behaviors, including reducing sensitivity to a devalued outcome, reducing breakpoint in progressive ratio, and shifting effort-related choice behavior. Separate cohorts of adult male and female C57BL/6 J mice were divided into Control or CNSDS groups, exposed to the 10-day CNSDS paradigm, and then trained and tested in instrumental reward or effort-related behaviors. CNSDS reduced motivation to lever press in progressive ratio and shifted effort-related choice behavior from a high reward to a more easily attainable low reward in both sexes. CNSDS caused more nuanced impairments in outcome devaluation. Taken together, CNSDS induces maladaptive shifts in effort-related choice and reduces motivated lever pressing in both sexes.

Functional anatomy of the bed nucleus of the stria terminalis-hypothalamus neural circuitry: Implications for valence surveillance, addiction, feeding, and social behaviors.

The bed nucleus of the stria terminalis (BNST) is a medial basal forebrain structure that modulates the hypothalamo-pituitary-adrenal (HPA) axis. The heterogeneous subnuclei of the BNST integrate inputs from mood and reward-related areas and send direct inhibitory projections to the hypothalamus. The connections between the BNST and hypothalamus are conserved across species, promote activation of the HPA axis, and can increase avoidance of aversive environments, which is historically associated with anxiety behaviors. However, BNST-hypothalamus circuitry is also implicated in motivated behaviors, drug seeking, feeding, and sexual behavior. These complex and diverse roles, as well its sexual dimorphism, indicate that the BNST-hypothalamus circuitry is an essential component of the neural circuitry that may underlie various psychiatric diseases, ranging from anorexia to anxiety to addiction. The following review is a cross-species exploration of BNST-hypothalamus circuitry. First, we describe the BNST subnuclei, microcircuitry and complex reciprocal connections with the hypothalamus. We will then discuss the behavioral functions of BNST-hypothalamus circuitry, including valence surveillance, addiction, feeding, and social behavior. Finally, we will address sex differences in morphology and function of the BNST and hypothalamus.

Dentate gyrus activin signaling mediates the antidepressant response.

Antidepressants that target monoaminergic systems, such as selective serotonin reuptake inhibitors (SSRIs), are widely used to treat neuropsychiatric disorders including major depressive disorder, several anxiety disorders, and obsessive-compulsive disorder. However, these treatments are not ideal because only a subset of patients achieve remission. The reasons why some individuals remit to antidepressant treatments while others do not are unknown. Here, we developed a paradigm to assess antidepressant treatment resistance in mice. Exposure of male C57BL/6J mice to either chronic corticosterone administration or chronic social defeat stress induces maladaptive affective behaviors. Subsequent chronic treatment with the SSRI fluoxetine reverses these maladaptive affective behavioral changes in some, but not all, of the mice, permitting stratification into persistent responders and non-responders to fluoxetine. We found several differences in expression of Activin signaling-related genes between responders and non-responders in the dentate gyrus (DG), a region that is critical for the beneficial behavioral effects of fluoxetine. Enhancement of Activin signaling in the DG converted behavioral non-responders into responders to fluoxetine treatment more effectively than commonly used second-line antidepressant treatments, while inhibition of Activin signaling in the DG converted responders into non-responders. Taken together, these results demonstrate that the behavioral response to fluoxetine can be bidirectionally modified via targeted manipulations of the DG and suggest that molecular- and neural circuit-based modulations of DG may provide a new therapeutic avenue for more effective antidepressant treatments.

Racial Diversity Among Histology of Renal Cell Carcinoma at an Urban Medical Center.

BACKGROUND: Non-Hispanic blacks (NHB) with renal cell carcinoma (RCC) are more likely to have papillary RCC (pRCC) than non-Hispanic whites (NHW). Data on histologic subtypes in RCC in Hispanics (H) are also sparse. Previous studies have shown that pRCC is more prevalent in NHB than in NHW, but they analyzed predominantly NHW populations. The Montefiore-Einstein Center for Cancer Care (MECC) serves a predominantly NHB and H population in the Bronx, NY. We investigated histologic subtype specific associations with established RCC risk factors in this population. PATIENTS AND METHODS: The MECC tumor registry was used to identify patients ≥ 18 years of age treated with partial or radical nephrectomy between January 2000 and December 2015. An institutional software program and individual chart review were used to obtain demographic data (including self-reported race, age, and sex), pathology data, and RCC risk factors (hypertension, diabetes, renal function, weight). Data were modeled by multinomial logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 1010 RCC cases were identified. Of these, 232 (23.0%) occurred in NHW, 383 (37.9%) NHB, 181 (17.9%) H, and 214 (21.2%) other. A total of 530 cases (52.5%) were clear cell (ccRCC) histology, 257 (25.4%) pRCC, 100 (9.9%) chromophobe (cRCC), and 123 (12.2%) other. Individuals with pRCC compared to ccRCC were more likely to be NHB than NHW (OR, 4.41; 95% CI, 2.81-6.93) but were less likely to be female (OR, 0.50; 95% CI, 0.35-0.72). Individuals with pRCC were also less likely to be H than NHW (OR, 0.52; 95% CI, 0.27-0.99). Patients with cRCC were also more likely to be NHB than NHW (OR, 2.23; 95% CI, 1.06-4.67). CONCLUSION: In the MECC data set, histology of RCC varies by race, confirming earlier reports that non-ccRCC is more common in NHB than NHW. We also report that pRCC is less common in H than NHW.

Factors Related to Diet Quality: A Cross-Sectional Study of 1055 University Students.

Given that there is only a limited body of evidence available concerning the dietary habits of Spanish university students, the present study assesses the quality of this group's diet, their adherence to the National Food-Based Dietary Guidelines, and the predictive factors of their diet quality. To do so, a cross-sectional study was performed on a sample of 1055 students. The quality of the participants' diets was then analysed by using the Spanish Healthy Eating Index, and then their level of compliance was assessed in light of the dietary recommendations put forth by the Spanish Society for Community Nutrition. According to these standards, only 17.4% of the participants had a healthy diet. The level of compliance with the recommendations was poor, highlighting especially the low levels of "fruit" and "vegetables" that they consumed as well as high levels of "cold meats and cuts" and "sweets". The factors that predicted a worse diet are being male, living alone, low levels of physical activity, smoking, high alcohol intake, leading a sedentary lifestyle, psychological distress, and insomnia (p < 0.005). Furthermore, participants with low or high body weights showed signs of a higher quality diet (p < 0.001). The present findings suggest that a significant proportion of university students ought to change their dietary habits; these also attest to the importance of developing strategies that are directly targeted at university students in order to promote a healthy diet.

Perception and Experience of Transcultural Care of Stakeholders and Health Service Users with a Migrant Background: A Qualitative Study.

INTRODUCTION: While European health policies do frequently take into consideration the ideas and experiences of their users, the voices of minority and marginalized communities are not often heard. European healthcare services must address this issue as the number of healthcare users with an MM background increases. AIM: To explore the perspectives of key stakeholders and healthcare users with an MM background on transcultural care in four European countries. DESIGN: Qualitative phenomenological study. METHODS: Semi-structured, individual interviews were conducted with stakeholders and MM users. Interviews were translated and transcribed verbatim and were carried out from February to May 2021. Descriptive statistics was used to describe the characteristics of the sample; qualitative data were analyzed thematically following Braun and Clarke's phases, resulting in 6 themes and 18 subthemes. RESULTS: For stakeholders and MM users with long-established residence in their respective countries, cultural differences involve different family and community norms, religious beliefs, lifestyles, and habits. These components are perceived as in tension with healthcare norms and values, and they mediate in two key and related aspects of the relationship between MM users and healthcare providers: accessibility and communication. CONCLUSIONS: Communication and access to healthcare are key to MM health service users, and they are the most frequent sources of misunderstanding and conflict between them and healthcare professionals. IMPACT: It is important to extend the investigation of cultural issues in healthcare to stakeholders and MM users. There is no doubt that healthcare professionals should be trained in cultural competence; however, cultural competence training is not the only area for improvement. There should be a change in paradigm in healthcare services across Europe: from individual to organizational integration of culture and diversity.

White matter microstructure and its relation to clinical features of obsessive-compulsive disorder: findings from the ENIGMA OCD Working Group.

Microstructural alterations in cortico-subcortical connections are thought to be present in obsessive-compulsive disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities. Here we investigated microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. We analyzed diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA OCD Working Group, in a cross-sectional case-control magnetic resonance study. We extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohen's d) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics. Adult OCD patients showed significant FA reduction in the sagittal stratum (d = -0.21, z = -3.21, p = 0.001) and posterior thalamic radiation (d = -0.26, z = -4.57, p < 0.0001). In the sagittal stratum, lower FA was associated with a younger age of onset (z = 2.71, p = 0.006), longer duration of illness (z = -2.086, p = 0.036), and a higher percentage of medicated patients in the cohorts studied (z = -1.98, p = 0.047). No significant association with symptom severity was found. Pediatric OCD patients did not show any detectable microstructural abnormalities compared to controls. Our findings of microstructural alterations in projection and association fibers to posterior brain regions in OCD are consistent with models emphasizing deficits in connectivity as an important feature of this disorder.

Chronic Stress Shifts Effort-Related Choice Behavior in a Y-Maze Barrier Task in Mice.

Mood disorders, including major depressive disorder, can be precipitated by chronic stress. The Y-maze barrier task is an effort-related choice test that measures motivation to expend effort and obtain reward. In mice, chronic stress exposure significantly impacts motivation to work for a higher value reward when a lesser value reward is freely available compared to unstressed mice. Here we describe the chronic corticosterone administration paradigm, which produces a shift in effortful responding in the Y-maze barrier task. In the Y-maze task, one arm contains 4 food pellets, while the other arm contains only 2 pellets. After mice learn to select the high reward arm, barriers with progressively increasing height are then introduced into the high reward arm over multiple test sessions. Unfortunately, most chronic stress paradigms (including corticosterone and social defeat) were developed in male mice and are less effective in female mice. Therefore, we also discuss chronic non-discriminatory social defeat stress (CNSDS), a stress paradigm we developed that is effective in both male and female mice. Repeating results with multiple distinct chronic stressors in male and female mice combined with increased usage of translationally relevant behavior tasks will help to advance the understanding of how chronic stress can precipitate mood disorders.

Chronic corticosterone shifts effort-related choice behavior in male mice.

RATIONALE: Effort-related choice tasks are used to study aspects of motivation in both rodents and humans (Der-Avakian and Pizzagalli Biol Psychiatry 83(11):932-939, 2018). Various dopaminergic manipulations and antidepressant treatments can shift responding to these tasks (Randall et al. Int J Neuropsychopharmacol 18(2), 2014; Yohn et al. Psychopharmacology 232(7):1313-1323, 2015). However, while chronic stress can precipitate mood disorders in humans, there is relatively little known about whether chronic stress elicits maladaptive behaviors in rodent effort-related choice tasks. OBJECTIVES: Chronic corticosterone (CORT) elicits an increase in negative maladaptive behaviors in male mice (David et al. Neuron 62(4):479-493, 2009; Gourley et al. Biol Psychiatry 64(10):884-890, 2008; Olausson et al. Psychopharmacology 225(3):569-577, 2013). We hypothesized that chronic CORT administration to male mice would reduce motivation for a higher effort, higher reward option, and shift responding to a less effortful, but a lesser reward. METHODS: Adult male C57BL/6J mice were administered either vehicle (n = 10) or CORT (n = 10) (~ 9.5 mg/kg/day) in their drinking water for 4 weeks, and then throughout all behavioral experiments (15 weeks total), and were tested in a Y-Maze barrier task and a fixed ratio concurrent (FR/chow) choice task. RESULTS: Chronic CORT reduced Y-maze HR arm choice when more effort was required to obtain the 4 food pellets (15-cm barrier in the high-reward (HR) arm, p < 0.001; 20-cm barrier in HR arm, p < 0.001) and shifted choice to the low reward (LR) arm where only 2 pellets were available. Chronic CORT also reduced lever pressing for food pellets in FR30/chow sessions of the concurrent choice task (p = 0.009), without impacting lab chow consumed. CONCLUSIONS: Chronic stress induces maladaptive shifts in effort-related choice behavior in the Y-maze barrier task in male mice. Furthermore, males subjected to chronic CORT administration show reduced lever pressing in FR30/chow sessions where lab chow is concurrently available. These data demonstrate that chronic corticosterone reduces motivation to work for and obtain a highly rewarding reinforcer when a lesser reinforcer is concurrently available.

Fluoxetine effects on behavior and adult hippocampal neurogenesis in female C57BL/6J mice across the estrous cycle.

RATIONALE: Some mood disorders, such as major depressive disorder, are more prevalent in women than in men. However, historically preclinical studies in rodents have a lower inclusion rate of females than males, possibly due to the fact that behavior can be affected by the estrous cycle. Several studies have demonstrated that chronic antidepressant treatment can decrease anxiety-associated behaviors and increase adult hippocampal neurogenesis in male rodents. OBJECTIVE: Very few studies have looked at the effects of antidepressants on behavior and neurogenesis across the estrous cycle in naturally cycling female rodents. METHODS: Here, we analyze the effects of chronic treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (Prozac) on behavior and adult hippocampal neurogenesis in naturally cycling C57BL/6J females across all four phases of the estrous cycle. RESULTS: In naturally cycling C57BL/6J females, fluoxetine decreases negative valence behaviors associated with anxiety in the elevated plus maze and novelty-suppressed feeding task, reduces immobility time in forced swim test, and increases adult hippocampal neurogenesis. Interestingly, the effects of fluoxetine on several negative valence behavior and adult hippocampal neurogenesis measures were mainly found within the estrus and diestrus phases of the estrous cycle. CONCLUSIONS: Taken together, these data are the first to illustrate the effects of fluoxetine on behavior and adult hippocampal neurogenesis across all four phases of the murine estrous cycle.