Effects of acute stress and cortisol on appetitive extinction: exploring the neuroendocrine mechanisms

• Applicant: Privatdozent Dr. Johannes Finke
• Subject Area: Biological Psychology and Cognitive Neuroscience
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 552126968

Stress has been linked to an increased risk for various mental disorders, in particular depression as well as other syndromes marked by altered reward processing such as addiction. Growing evidence suggests a crucial role of stress-induced changes in learning and memory as a mediator of this relationship. However, well-known effects of stress on dopaminergic networks notwithstanding, the pathways by which acute stress influences reward learning are still poorly understood, and existing evidence is partly inconsistent. In particular, there is an eminent lack of human research on the causal role of stress hormones in the modulation of appetitive Pavlovian conditioning under stress. The present project thus aims to clarify how cortisol acutely affects the processing of the incentive value of appetitively conditioned stimuli (CS) and whether this depends on the latency of CS exposure relative to stress. The first projected study will investigate this question based on a pharmacological design that allows for disentangling genomic vs. non-genomic hormonal effects. To this end, a sample of healthy male participants will first acquire conditioned responses (CRs) to different auditory cues by means of a standard appetitive learning paradigm. After that, metyrapone (750 mg) will be administered orally to inhibit endogenous cortisol production. Prior to repeated CS presentation (performed partly under extinction), a moderate dose of either cortisol (5 mg) or placebo (NaCl) will be given intravenously at two time points (60 vs. 10 min before extinction). Specifically, one group of participants will receive placebo at both times (control group), whereas another group will be administered cortisol first and then placebo (‘genomic’ group). Conversely, a third group will be given placebo first and then cortisol (‘non-genomic’ group). Based on a gender-mixed sample, the second study will aim to corroborate and extend the results of the first experiment using a naturalistic stressor instead of a pharmacological intervention (socially evaluated cold pressor test vs. warm-water exposure) for eliciting cortisol responses (70 vs. 20 min prior to extinction). Moreover, this study will explore a potential interplay of cortisol with adrenergic activation during stress. During both learning phases, pupil dilation responses and further autonomic markers will be recorded as dependent measures to track learning processes. Relatively reduced extinction of CRs (indexing enhanced incentive salience) is expected in the non-genomic group (Study I) as well as immediately after stress (Study II). Taken together, the proposed project will address several important research gaps in this emerging field and is likely to provide new insights into the mechanisms underlying the relationship between reward learning and stress, which will contribute to a deeper understanding of the pathogenesis of stress-related disorders as well as inform novel approaches to treatment and prevention.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Tim Klucken