Preprint: Alcohol Stress Response Dampening during imminent vs. distal, uncertain threat

Research indicates that fear and anxiety are distinct processes with separable neurobiological substrates. Predictable vs. unpredictable shock administration has been used to elicit fear vs. anxiety, respectively. Recent research has demonstrated that alcohol may reduce anxiety but not fear. However, previous manipulations of predictability have varied both probability and temporal uncertainty of shock threat, leaving unresolved questions regarding which stimulus characteristics elicit anxiety and are sensitive to alcohol stress response dampening (SRD). We developed a novel paradigm to closely parallel basic research in animals that systematically varied temporal uncertainty of threat while holding threat probability constant. Intoxicated (0.08% target BAC), placebo, and no-alcohol control participants viewed a series of visual threat cues. Certain cue duration (5 seconds) blocks were equivalent to predictable shock blocks eliciting fear in earlier research. Uncertain cue duration (5, 20, 50 or 80 second, intermixed) blocks introduced temporal uncertainty regarding impending shock to elicit anxiety. Startle potentiation relative to matched cue periods in no-shock blocks provided the primary measure of affective response. All threat cues produced robust startle potentiation. Alcohol reduced startle potentiation during the first 5 seconds of threat cue presentation in uncertain but not certain duration blocks. Alcohol also reduced startle potentiation at later times among longer uncertain duration cues, suggesting that alcohol SRD persisted. Trait negative emotionality and binge drinking status moderated alcohol SRD magnitude during uncertain threat. These translational findings corroborate previous reports regarding distinct substrates of fear vs. anxiety, and have implications for both alcoholism etiology and comorbidity with anxiety disorders.