Study information published in Cell describe the improvement of a biosensor that permits for the monitoring of serotonin dynamics in the brain in true time. Using this biosensor, researchers had been in a position to investigate a novel psychedelic compound that seems to ameliorate depressive symptoms without having inducing hallucinogenic experiences.
Although specific psychedelic compounds have displayed guarantee for the therapy of depression, it remains unclear irrespective of whether the therapeutic properties of these compounds can be separated from the hallucinogenic effects. Psychedelic compounds most typically target the 5-hydroxytryptamine 2A receptor (5-HT2AR) in neurons and exert influence by binding the receptor and altering its shape. Different conformational modifications map to diverse psychological effects.
To much better comprehend the conformational effects of psychedelic compounds, researchers created psychLight, a genetically encoded biosensor that generates fluorescence in 5-HT2AR.
The genetic code for a fluorescent protein was inserted into the genome of murine models. The capacity of psychLight to detect hallucinogenic compounds was tested by comparing psychLight’s output to mouse behavior immediately after compound administration. Rodents show a characteristic “head-twitch” motion when exposed to hallucinogenic compounds. In trials of a number of hallucinogenic and non-hallucinogenic drugs, psychLight’s improved fluorescence correlated strongly with the “head-twitch” response. Drugs that did not generate a twitching response also did not seem fluorescent with psychLight. This close correlation involving mouse behavior and psychLight output supports the efficacy of the biosensor to determine hallucinogenic properties in myriad compounds.
One compound studied in the course of psychLight trials, AAZ-A-154, appeared to cut down depression symptoms without having creating hallucinogenic effects. Mice treated with AAZ-A-154 did not show either any head twitches or any fluorescence with psychLight. During in vitrostudies of cultured rat embryonic cortical neurons, AAZ-A-154 appeared to “promote dendritic outgrowth” and raise “dendritic…complexity” in a manner related to the antidepressant ketamine. AAZ-A-154 also appeared to lower anhedonic behavior in mice as demonstrated by their decreased immobility in the course of forced swim tests and improved interest in a sweetened water resolution.
The improvement of psychLight may well allow future researchers to test the possible hallucinogenic properties of novel therapeutic compounds. PsychLight also displays possible for the monitoring of serotonin dynamics in true time, which could much better inform the nature of depression and its response to psychedelic drugs. Further study of the compound AAZ-A-154 is also warranted.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device corporations. Please see the original reference for a complete list of authors’ disclosures.
Dong C, Ly C, Dunlap LE, et al. Psychedelic-inspired drug discovery using an engineered biosensor. Cell. Published on the net May 13, 2021. doi:10.1016/j.cell.2021.03.043