Social defeat stress: Mechanisms underlying the increase in rewarding effects of drugs of abuse

Social interaction is known to be the main source of stress in human beings, which explains the translational importance of this research in animals. Evidence reported over the last decade has revealed that, when exposed to social defeat experiences (brief episodes of social confrontations during adolescence and adulthood), the rodent brain undergoes remodeling and functional modifications, which in turn lead to an increase in the rewarding and reinstating effects of different drugs of abuse. The mechanisms by which social stress cause changes in the brain and behavior are unknown, and so the objective of this review is to contemplate how social defeat stress induces long-lasting consequences that modify the reward system. First of all, we will describe the most characteristic results of the short- and long-term consequences of social defeat stress on the rewarding effects of drugs of abuse such as psychostimulants and alcohol. Secondly, and throughout the review, we will carefully assess the neurobiological mechanisms underlying these effects, including changes in the dopaminergic system, corticotrophin releasing factor signaling, epigenetic modifications and the neuroinflammatory response. To conclude, we will consider the advantages and disadvantages and the translational value of the social defeat stress model, and will discuss challenges and future directions

Diagnostic routes and time intervals for patients with colorectal cancer in 10 international jurisdictions; findings from a cross-sectional study from the International Cancer Benchmarking Partnership (ICBP)

OBJECTIVE: International differences in colorectal cancer (CRC) survival and stage at diagnosis have been reported previously. They may be linked to differences in time intervals and routes to diagnosis. The International Cancer Benchmarking Partnership Module 4 (ICBP M4) reports the first international comparison of routes to diagnosis for patients with CRC and the time intervals from symptom onset until the start of treatment. Data came from patients in 10 jurisdictions across six countries (Canada, the UK, Norway, Sweden, Denmark and Australia). DESIGN: Patients with CRC were identified via cancer registries. Data on symptomatic and screened patients were collected; questionnaire data from patients\u27 primary care physicians and specialists, as well as information from treatment records or databases, supplemented patient data from the questionnaires. Routes to diagnosis and the key time intervals were described, as were between-jurisdiction differences in time intervals, using quantile regression. PARTICIPANTS: A total of 14 664 eligible patients with CRC diagnosed between 2013 and 2015 were identified, of which 2866 were included in the analyses. PRIMARY AND SECONDARY OUTCOME MEASURES: Interval lengths in days (primary), reported patient symptoms (secondary). RESULTS: The main route to diagnosis for patients was symptomatic presentation and the most commonly reported symptom was \u27bleeding/blood in stool\u27. The median intervals between jurisdictions ranged from: 21 to 49 days (patient); 0 to 12 days (primary care); 27 to 76 days (diagnostic); and 77 to 168 days (total, from first symptom to treatment start). Including screen-detected cases did not significantly alter the overall results. CONCLUSION: ICBP M4 demonstrates important differences in time intervals between 10 jurisdictions internationally. The differences may justify efforts to reduce intervals in some jurisdictions