Investigating the role of the central and the peripheralbenzodiazepine receptor on stress and anxiety relatedparameters
Year: 2020
Type: dissertation
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Anxiety disorders belong to the most prevalent mental disorders worldwide implying a high burden of illness. Due to their complexity and variety of underlying dysfunctions, it remains a challenging task to find optimum pharmacological treatment. Benzodiazepines, which modulate the GABAA or central benzodiazepine receptor, are among the most frequently used substances in this field. However, they hold several side effects, especially at longer application. In the search for alternatives, substances that target the translocator protein (TSPO), also known as peripheral benzodiazepine receptor, yield promising candidates. Within the present work, we aimed to compare the effects of a benzodiazepine and a TSPO ligand, which further binds to GABAA receptors, on stress and anxiety related parameters. \nWithin a randomized clinical trial, 60 healthy male subjects received either a daily dose of 1.5 mg alprazolam, 150 mg etifoxine or placebo for a period of five days. We applied the Trier Social Stress Test in Virtual Reality, the NPU Threat Test, resting-state functional imaging, and the Continuous Performance Test and assessed self-reports, physiological parameters, salivary and blood markers, objective performance parameters as well as changes of functional brain connectivity. \nWhile alprazolam blunted the response of the HPA axis to acute psychosocial stress, etifoxine increased expression of TSPO independent of additional external stimulation. There were no effects of the medication on subjective or physiological measures of the stress response. Neither alprazolam nor etifoxine had an impact on the anxiety-related startle reflex, while etifoxine attenuated the fear-potentiated startle on day 1 of treatment. Alprazolam increased functional neuronal connectivity within and between several resting- state networks. In neither group, there was strong impairment of alertness or any serious adverse event or study dropout. When focusing on symptoms related to sedation, there were more reports from subjects that had received alprazolam. \nThe present work revealed different effects of the applied substances on molecular, physiological and neuronal markers of stress and anxiety. Thereby, especially the strength with which the GABAergic system is affected seems to play an important role, while the involvement of TSPO might be rather specific and dependent on the respective pathological state.
Author: Lisa‐Marie Bahr
Language: English
Subfield: Behavioral Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3117593711