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Rationale: Balancing approach of positive and avoidance of negative stimuli is essential when faced with approach-avoidance conflicts, e.g., situations with both positive and negative outcomes. This balance is disturbed in several mental disorders, e.g., excessive avoidance in anxiety disorders, and heightened approach in substance use disorders. Since stress is assumed to impact these disorders' etiology and maintenance, it seems crucial to understand how stress influences behavior in approach-avoidance conflicts. Indeed, some studies suggested altered approach-avoidance behavior under acute stress, but the mechanism underlying these effects is unknown., Objectives: Investigate how the pharmacological manipulation of major stress mediators (cortisol and noradrenaline) influences task-based approach-avoidance conflict behavior in healthy individuals., Methods: Ninety-six participants (48 women, 48 men) received either 20mg hydrocortisone, 20mg yohimbine, both, or placebo before performing a task targeting foraging under predation in a fully crossed double-blind between-subject design. Moreover, we investigated effects of gender and endogenous testosterone and estradiol levels on approach-avoidance behavior., Results: While biological stress markers (cortisol concentration, alpha amylase activity) indicated successful pharmacological manipulation, behavior in approach-avoidance conflicts was not affected as expected. Although yohimbine administration affected risky foraging latency under predation, we found no main effect of hydrocortisone or their interaction on behavior. In contrast, we found gender differences for almost all behavioral outcome measures, which might be explained by differences in endogenous testosterone levels., Conclusions: The investigated major stress mediators were not sufficient to imitate previously shown stress effects on approach-avoidance conflict behavior. We discuss potential reasons for our findings and implications for future research., (© 2023. The Author(s).)

The superior colliculus (SC) contains an auditory space map that is shaped by projections from several subcortical auditory nuclei. Both GABAergic (inhibitory) and excitatory cells contribute to these inputs, but there are contradictory reports regarding the sources of these inputs. We used retrograde tracing techniques in guinea pigs to identify cells in the auditory brainstem that project to the SC. We combined retrograde tracing with immunohistochemistry for glutamic acid decarboxylase (GAD) to identify putative GABAergic cells that participate in this pathway. Following a tracer injection in the SC, the nucleus of the brachium of the inferior colliculus (NBIC) contained the most labeled cells, followed by the inferior colliculus (IC). Smaller populations were observed in the sagulum, paralemniscal area, periolivary nuclei and ventrolateral tegmental nucleus. Overall, only 10% of the retrogradely labeled cells were GAD immunopositive. The presumptive inhibitory cells were observed in the NBIC, IC, superior paraolivary nucleus, sagulum and paralemniscal area. We conclude that the guinea pig SC receives input from a diverse set of auditory brainstem nuclei, some of which provide GABAergic input. These diverse origins of input to the SC likely represent a variety of functions. Inputs from the NBIC and IC likely provide spatial information for guiding orienting behaviors. Inputs from subcollicular nuclei are less likely to provide spatial information; rather, they may provide a shorter route for auditory information to reach the SC, and could generate avoidance or escape responses to an external threat.