Freezing is a species-typical defensive reaction to conditioned threats. While the neural circuitry of aversive Pavlovian behavior has been extensively studied, less is known about the circuitry underlying more active responses to danger. Here we show that the flow of information between the basal amygdala (BA) and the nucleus accumbens (NAcc) is necessary for signaled active avoidance behavior. Rats trained to avoid shock by shuttling during an auditory conditioned stimulus showed increased expression of the activity-dependent protein c-Fos in the NAcc, specifically the shell subregion (NAccSh). Silencing neural activity in the NAccSh, but not in the adjacent NAcc core, disrupted avoidance behavior. Disconnection of the BA and the NAccSh was just as effective at disrupting avoidance behavior as bilateral NAccSh inactivations, suggesting learned avoidance behavior requires an intact BA-NAccSh circuit. Together, these data highlight an essential role for the amygdalar projection to the ventral striatum in aversively motivated actions.

Traumatic events are proposed to play a role in the development of anxiety disorders, however not all individuals exposed to extreme stress experience a pathological increase in fear. Recent studies in animal models suggest that the degree to which one is able to control an aversive experience is a critical factor determining its behavioral consequences. In this study, we examined whether stressor controllability modulates subsequent conditioned fear expression in humans. Participants were randomly assigned to an escapable stressor condition, a yoked inescapable stressor condition, or a control condition involving no stress exposure. One week later, all participants underwent fear conditioning, fear extinction, and a test of extinction retrieval the following day. Participants exposed to inescapable stress showed impaired fear extinction learning and increased fear expression the following day. In contrast, escapable stress improved fear extinction and prevented the spontaneous recovery of fear. Consistent with the bidirectional controllability effects previously reported in animal models, these results suggest that one's degree of control over aversive experiences may be an important factor influencing the development of psychological resilience or vulnerability in humans.

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Rationale Pavlovian conditioned responses to cues that signal threat are rapidly acquired and tend to persist over time. However, recent research suggests that the ability to actively avoid or exert control over an anticipated threat can diminish the subsequent expression of Pavlovian responses. Studies in animal models suggest that active avoidance behavior and its consequences may be mediated by dopaminergic function. In the present study, we sought to replicate the finding that active control over threat can attenuate subsequent Pavlovian responding in humans and conducted exploratory analyses testing whether individual differences in blink rate, a putative index of dopaminergic function, might modulate this effect. Methods Participants underwent Pavlovian aversive conditioning, followed immediately by one of two conditions. In the active avoidance condition, participants had the opportunity to actively prevent the occurrence of an anticipated shock, whereas in a yoked extinction condition, participants passively observed the cessation of shocks, but with no ability to influence their occurrence. The following day, the conditioned stimuli were presented without shock, but both groups of participants had no opportunity to employ active instrumental responses. Blink rate was measured throughout the task, and skin conductance responses served as our index of Pavlovian conditioned responding. Results Consistent with our previous findings, we observed that the group that could actively avoid the shock on day 1 exhibited attenuated recovery of Pavlovian conditioned responses. Further, we found that individuals in the active avoidance group with higher blink rates exhibited a more robust attenuation of spontaneous recovery. Conclusion This finding suggests that individual variation in dopaminergic function may modulate the efficacy with which active avoidance strategies can attenuate reactive Pavlovian responses. Electronic supplementary material The online version of this article (10.1007/s00213-018-5082-6) contains supplementary material, which is available to authorized users.

Background The Eliminate Hepatitis C San Diego County Initiative was established to provide a roadmap to reduce new HCV infections by 80% and HCV-related deaths by 65% by 2030. An estimate of the burden of HCV infections in San Diego County is necessary to inform planning and evaluation efforts. Our analysis was designed to estimate the HCV burden in San Diego County in 2018. Methods We synthesized data from the American Community Survey, Centers for Disease Control and Prevention, California Department of Public Health, Public Health Branch of California Correctional Health Care Services, San Diego Blood Bank, and published literature. Burden estimates were stratified by subgroup (people who inject drugs in the community [PWID], men who have sex with men in the community [MSM], general population in the community [stratified by age and sex], and incarcerated individuals). To account for parameter uncertainty, 100,000 parameter sets were sampled from each parameter’s uncertainty distribution, and used to calculate the mean and 95% confidence interval estimates of the number of HCV seropositive adults in San Diego in 2018. Findings We found there were 55,354 (95% CI: 25,411–93,329) adults with a history of HCV infection in San Diego County in 2018, corresponding to an HCV seroprevalence of 2.1% (95% CI: 1.1–3.4%). Over 40% of HCV infections were among the general population aged 55–74 and one-third were among PWID. Conclusion Our study found that the largest share of infections was among adults aged 55–74, indicating the importance of surveillance, prevention, testing, and linkages to care in this group to reduce mortality. Further, programs prioritizing PWID for increased HCV testing and linkage to care are important for reducing new HCV infections.