Targeting α7 Nicotinic Acetylcholine Receptors in Post-Traumatic Stress Disorder: Mechanisms and Clinical Implications

Post-traumatic stress disorder (PTSD) is a severe disorder that is characterized by intrusive thoughts, impaired mood and cognition, hyperarousal, and avoidance in the months and years following a traumatic event. PTSD is comorbid with depression, anxiety, substance abuse, and is challenging for the treatment with psycho- and pharmacotherapy. In light of novel neurobiological findings on the pathogenesis of the disease, innovative approaches to its treatment are investigated. Recently, targeting cholinergic signaling with an antagonist of α7 nicotinic acetylcholine receptors (nAChR), BNC-210, showed a significant promise in clinical trials. This opened up a novel therapeutic strategy that, considering its translational success, calls for a mechanistic understanding. In this review, we dissect the neurobiological role of α7 nAChR in regard of PTSD, and related depression and anxiety states. We discuss the synaptic role of the receptor in fear circuits, immune and endocrine role via the anti-inflammatory cholinergic pathway, and current evidence for the utility of pharmacological modulation of α7 nAChR.