A Key Role for Neurotensin in Chronic-Stress-Induced Anxiety-Like Behavior in Rats

Accepted ManuscriptChronic stress is a major cause of anxiety disorders that can be reliably modeled preclinically, providing insight into alternative therapeutic targets for this mental health illness. Neuropeptides have been targeted in the past to no avail possibly due to our lack of understanding of their role in pathological models. In this study we use a rat model of chronic stress-induced anxiety-like behaviors and hypothesized that neuropeptidergic modulation of synaptic transmission would be altered in the bed nucleus of the stria terminalis (BNST), a brain region suspected to contribute to anxiety disorders. We use brain slice neurophysiology and behavioral pharmacology to compare the role of locally released endogenous neuropeptides on synaptic transmission in the oval (ov) BNST of non-stressed (NS) or chronic unpredictably stressed (CUS) rats. We found that in NS rats, post-synaptic depolarization induced the release of vesicular neurotensin (NT) and corticotropin-releasing factor (CRF) that co-acted to increase ovBNST inhibitory synaptic transmission in 59% of recorded neurons. CUS bolstered this potentiation (100% of recorded neurons) through an enhanced contribution of NT over CRF. In contrast, locally released opioid neuropeptides decreased ovBNST excitatory synaptic transmission in all recorded neurons, regardless of stress. Consistent with CUS-induced enhanced modulatory effects of NT, blockade of ovBNST NT receptors completely abolished stress-induced anxiety-like behaviors in the elevated plus maze paradigm. The role of NT has been largely unexplored in stress and our findings highlight its potential contribution to an important behavioral consequence of chronic stress, that is, exaggerated avoidance of open space in rats.CPN was funded by CIHR Vanier Graduate Scholarship (338319); APVS was funded by Fundação para a Ciência e Tecnologia (SFRH/BPD/52078/2013); ERH was funded by CIHR Postdoctoral Fellowship (MFE-123712); SA was funded by a Queen Elizabeth II Graduate Scholarship in Science and Technology; ÉCD was funded by the Canadian Institute of Health Research (MOP-25953)info:eu-repo/semantics/publishedVersio

The 16th Data Release of the Sloan Digital Sky Surveys: First Release from the APOGEE-2 Southern Survey and Full Release of eBOSS Spectra

This paper documents the 16th data release (DR16) from the Sloan Digital Sky Surveys (SDSS), the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the Southern Hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey and new data from the SPectroscopic IDentification of ERosita Survey programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library "MaStar"). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17)

The 16th Data Release of the Sloan Digital Sky Surveys: First Release from the APOGEE-2 Southern Survey and Full Release of eBOSS Spectra

This paper documents the 16th data release (DR16) from the Sloan Digital Sky Surveys (SDSS), the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the Southern Hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey and new data from the SPectroscopic IDentification of ERosita Survey programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library "MaStar"). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17)

The 16th Data Release of the Sloan Digital Sky Surveys : First Release from the APOGEE-2 Southern Survey and Full Release of eBOSS Spectra

This paper documents the 16th data release (DR16) from the Sloan Digital Sky Surveys (SDSS), the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the Southern Hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey and new data from the SPectroscopic IDentification of ERosita Survey programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library "MaStar"). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17).Peer reviewe

Prevalence of cannabis withdrawal symptoms among people with regular or dependent use of cannabinoids: a systematic review and meta-analysis.

Importance: Cannabis withdrawal syndrome (CWS)-a diagnostic indicator of cannabis use disorder-commonly occurs on cessation of heavy and prolonged cannabis use. To date, the prevalence of CWS syndrome has not been well described, nor have the factors potentially associated with CWS. Objectives: To estimate the prevalence of CWS among individuals with regular or dependent use of cannabinoids and identify factors associated with CWS. Data Sources: A search of literature from database inception to June 19, 2019, was performed using MEDLINE, Embase, PsycINFO, Web of Science, the Cumulative Index to Nursing and Allied Health Literature, ProQuest, Allied and Complementary Medicine, and Psychiatry online, supplemented by manual searches of reference lists of included articles. Articles were included if they (1) were published in English, (2) reported on individuals with regular use of cannabinoids or cannabis use disorder as a primary study group, (3) reported on the prevalence of CWS or CWS symptoms using a validated instrument, (4) reported the prevalence of CWS, and (5) used an observational study design (eg, cohort or cross-sectional). All abstracts, full-text articles, and other sources were reviewed, with data extracted in duplicate. Cannabis withdrawal syndrome prevalence was estimated using a random-effects meta-analysis model, alongside stratification and meta-regression to characterize heterogeneity. Main Outcomes and Measures: Cannabis withdrawal syndrome prevalence was reported as a percentage with 95% CIs. Results: Of 3848 unique abstracts, 86 were selected for full-text review, and 47 studies, representing 23 518 participants, met all inclusion criteria. Of 23 518 participants included in the analysis, 16 839 were white (72%) and 14 387 were men (69%); median (SD) age was 29.9 (9.0) years. The overall pooled prevalence of CWS was 47% (6469 of 23 518) (95% CI, 41%-52%), with significant heterogeneity between estimates (I2 = 99.2%). When stratified by source, the prevalence of CWS was 17% (95% CI, 13%-21%) in population-based samples, 54% in outpatient samples (95% CI, 48%-59%), and 87% in inpatient samples (95% CI, 79%-94%), which were significantly different (P < .001). Concurrent cannabis (β = 0.005, P < .001), tobacco (β = 0.002, P = .02), and other substance use disorders (β = 0.003, P = .05) were associated with a higher CWS prevalence, as was daily cannabis use (β = 0.004, P < .001). Conclusions and Relevance: These findings suggest that cannabis withdrawal syndrome appears to be prevalent among regular users of cannabis. Clinicians should be aware of the prevalence of CWS in order to counsel patients and support individuals who are reducing their use of cannabis

Transcranial Magnetic Stimulation of the Supplementary Motor Area in the Treatment of Obsessive-Compulsive Disorder: A Multi-Site Study

Recently, strategies beyond pharmacological and psychological treatments have been developed for the management of obsessive-compulsive disorder (OCD). Specifically, repetitive transcranial magnetic stimulation (rTMS) has been employed as an adjunctive treatment in cases of treatment-refractory OCD. Here, we investigate six weeks of low frequency rTMS, applied bilaterally and simultaneously over the sensory motor area, in OCD patients in a randomized, double-blind placebo-controlled clinical trial. Twenty-two participants were randomly enrolled into the treatment (ACTIVE = 10) or placebo (SHAM = 12) groups. At each of seven visits (baseline; day 1 and weeks 2, 4, and 6 of treatment; and two and six weeks after treatment) the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was administered. At the end of the six weeks of rTMS, patients in the ACTIVE group showed a clinically significant decrease in Y-BOCS scores compared to both the baseline and the SHAM group. This effect was maintained six weeks following the end of rTMS treatment. Therefore, in this sample, rTMS appeared to significantly improve the OCD symptoms of the treated patients beyond the treatment window. More studies need to be conducted to determine the generalizability of these findings and to define the duration of rTMS’ clinical effect on the Y-BOCS. Clinical Trial Registration Number (NCT) at www.clinicaltrials.gov: NCT00616486

The effects of social isolation on schedule induced polydipsia (SIP).

<p>(A) Isolation rearing (IR) housing significantly increased drinking in the schedule induced polydipsia paradigm across days. Mean (±SEM) daily water drinking during the 2-hr testing session for IR and group reared (GR) groups in the experimental paradigm are shown. IR animals were not different from GR animals on Day 1 of testing (F<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056105#pone.0056105-deLeon1" target="_blank">[1]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056105#pone.0056105-Beninger1" target="_blank">[14]</a> = 2.8, p = 0.12) but on Day 21 drank more water than the GR group (F<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056105#pone.0056105-deLeon1" target="_blank">[1]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056105#pone.0056105-Beninger1" target="_blank">[14]</a> = 6.2, p = 0.04). (B) Intermittent food presentation increased time spent at the drinking spout. Mean (±SEM) duration (ms) spent at the drinking spout during the inter-pellet interval (1 min; measured in 5-s bins) for IR and GR groups. Both groups increased spout time to a maximum within 10-s following pellet delivery and decreased time toward the end of the interval. This pattern was more pronounced in the IR group suggesting increased drinking behavior. *Two-way analysis of variance, significant interaction of day×housing (F[20,260] = 2.76, p = 0.047).</p

Experimental design: number of rats assigned to each group for each experiment.

<p>Abbreviations: GR, group reared; IR, isolation reared; n/a, no animals in these groups; SIP, schedule-induced polydipsia.</p

Proportion of animals that achieved schedule-induced polydipsia (drinking at least 15 ml per 2-hr session on 3 consecutive days) collapsed across MK-801 treatment in experiment 2.

*<p>Significantly more isolation-reared animals (collapsed across treatment) achieved schedule-induced polydipsia than group-reared animals, Chi-square test, p<0.01.</p