Phasic changes in the activity of midbrain dopamine cells motivate and guide future behavior. Activation of the lateral habenula by aversive events inhibits dopamine neurons transiently, providing a neurobiological representation of learning models that incorporate negative reward prediction errors. Anatomical evidence suggests that this inhibition occurs via the rostromedial tegmental nucleus, but this hypothesis has yet to be tested directly. Here, we show that axon-sparing lesions of the rostromedial tegmentum attenuate habenula-induced inhibition of dopamine neurons significantly. These data support a substantial role for the rostromedial tegmentum in habenula-induced feedforward inhibition of dopamine neurons.
In a prospective study of street-based female sex workers in Baltimore, Maryland, recent entry into sex work, sexual violence, having same-sex partners elevated STI risk.
Background: Despite experiencing HIV/STIs, violence, and other morbidities at higher rates than the general public, street-based female sex workers are often absent from public health research and surveillance due to the difficulty and high costs associated with engagement and retention. The current study builds on existing literature by examining barriers and facilitators of retaining a street-based cohort of cisgender female sex workers recruited in a mobile setting in Baltimore, Maryland who participated in the SAPPHIRE study. Participants completed interviews and sexual health testing at baseline, 3-, 6-, 9-, and 12-months. Methods: Retention strategies are described and discussed in light of their benefits and challenges. Strategies included collecting several forms of participant contact information, maintaining an extensive field presence by data collectors, conducting social media outreach and public record searches, and providing cash and non-cash incentives. We also calculated raw and adjusted retention proportions at each follow-up period. Lastly, baseline sample characteristics were compared by number of completed visits across demographic, structural vulnerabilities, work environment, and substance use variables using F-tests and Pearson's chi-square tests. Results: Although there were drawbacks to each retention strategy, each method was useful in tandem in achieving a successful follow-up rate. While direct forms of contact such as phone calls, social media outreach, and email were useful for retaining more stable participants, less stable participants required extensive field-based efforts such as home and site visits that increase the likelihood of random encounters. Overall, adjusted retention exceeded 70% for the duration of the 12-month study. Participants who were younger, recently experienced homelessness, and injected drugs daily were less likely to have completed all or most follow-up visits. Conclusion: Retention of street-based female sex workers required the simultaneous use of diverse retention strategies that were tailored to participant characteristics. With familiarity of the dynamic nature of the study population characteristics, resources can be appropriately allocated to strategies most likely to result in successful retention.
Rationale
Processes of attention have a heritable component, suggesting that genetic predispositions may predict variability in the response to attention-enhancing drugs. Among lead compounds with attention-enhancing properties are nicotinic acetylcholine receptor (nAChR) agonists.
Objectives
To test, by comparing three rat strains, whether genotype may influence the sensitivity to nicotine in the 5-Choice Serial Reaction Time Task (5-CSRTT), a rodent model of attention.
Methods
Strains tested were Long Evans (LE), Sprague Dawley (SD), and Wistar rats. The 5-CSRTT requires responses to light stimuli presented randomly in one of five locations. The effect of interest was an increased percentage of responses in the correct location (accuracy), the strongest indicator of improved attention.
Results
Nicotine (0.05–0.2 mg/kg s.c.) reduced omission errors and response latency and increased anticipatory responding in all strains. In contrast, nicotine dose-dependently increased accuracy in Wistar rats only. The nAChR antagonist mecamylamine (0.75–3 mg/kg s.c.) increased omissions, slowed responses, and reduced anticipatory responding in all strains. There were no effects on accuracy, which was surprising giving the clear improvement with nicotine in the Wistar group.
Conclusions
The findings suggest strain differences in the attention-enhancing effects of nicotine, which would indicate that genetic predispositions predict variability in the efficacy of nAChR compounds for enhancing attention. The absence of effect of mecamylamine on response accuracy may suggest a contribution of nAChR desensitization to the attention-enhancing effects of nicotine.
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