Stress pervades modern life. It affects various brain functions, posing risks for many psychiatric disorders. However, few therapeutics are available to combat such deleterious effects of stress. One class of candidate drugs are psychedelics. With potent effects on the human mind, these drugs have received renewed research interest in recent years. However, their hallucinogenic effects remain a concern for clinical applications. Using a mouse model of unpredictable mild stress, we investigated a novel compound called tabernanthalog (TBG), which is similar in structure to the psychedelic drug ibogaine but free from its hallucinogenic and toxic effects. We found that a single low dose of TBG can correct stress-induced behavioral deficits including anxiety, cognitive inflexibility, and defective sensory processing. In the stressed brain, TBG promotes the regrowth of stress-disrupted connections between cortical neurons and normalizes their activity patterns. In a follow up study, we compared the behavioral impact of TBG and 2,5-Dimethoxy-4-iodoamphetamine (DOI, a hallucinogenic psychedelic) using a computational neuroethology approach. We found that DOI induces certain behavioral motifs in mice, and persistently reduces the complexity of spontaneous behavioral sequences, whereas TBG does not. Our study highlights the potential of using analogs of psychedelics to treat stress-related brain disorders and provides novel insights into the neural mechanisms underlying their therapeutic effects.
Dr. Ju Lu seeks to understand how neural circuits are organized and modified in response to experiences, leveraging diverse imaging techniques to study the structural and functional dynamism of the nervous system across spatiotemporal scales, from synapses and neuronal assemblies to the whole-cortex network. He received a B. Eng. in microelectronics from Tsinghua University in China and a Ph.D. in neurobiology from Harvard University. He did a postdoc at Stanford University and worked as a research scientist at University of California Santa Cruz before joining Lehigh University. His recent research focused on how psychedelics and their analogs modulate normal behavior and rescue stress-induced deficits in neural circuits and behavior.