Genetic dissection of the neuronal circuit through which serotonin 2a receptor activation modulates fear expression. (FWOKN284)

Anxiety and fear are normal emotional responses to threats but these emotions can become maladaptive, and interfere with daily life. Chronic and excessive emotional distress and fear are key features of anxiety disorders, the most common cause of psychiatric illness. Exposure therapy, aimed at curbing excessive fear, is associated with decreased symptom severity, but up to 40% of patients show only partial long-term benefit and a majority of do not become fully free of symptoms. This sparked the interest towards drug-assisted psychotherapy. Hallucinogens such as lysergic acid diethylamide or LSD, are reconsidered for therapeutic use in anxiety disorders. A recent study demonstrated that LSD may reduce anxiety in patients with life-threatening diseases. However, it remains poorly understood through what mechanism hallucinogens could facilitate psychotherapy. Hallucinogens are agonists of the serotonin 2a receptor. We found that activation of this receptor by a hallucinogenic drug can dramatically reduce fear expression in mice. We pinpointed the amygdala, a part of the brain that is critically involved in emotional regulation, as a key target site for the observed effects on fear expression. We aim to provide a better understanding on how 5-HT2a receptors modulate fear processing and will improve the neurobiological framework against which potential hallucinogen-assisted psychotherapy for anxiety disorders should be evaluated.

Keywords:Fear

Disciplines:Pharmacology not elsewhere classified, Chemical product design and formulation