Fully automated head-twitch detection system for the study of 5-HT2A receptor pharmacology in vivo
Scientific Reports – October 03, 2019
Source: OpenAlex
Summary
An antipsychotic drug in development effectively blocks the head-twitch behavior (HTR) characteristic of psychedelics. This Neuroscience insight for Psychedelics and Drug Studies emerged from a new fully automated system for detecting HTR, enhancing Biochemical Analysis and Sensing Techniques. It revealed that an Agonist targeting the metabotropic glutamate receptor 2 (a type of Metabotropic receptor) significantly reduced HTR. Conversely, blocking this Metabotropic glutamate receptor potentiated psychedelic effects. This Pharmacology, aided by Computer science, advances understanding of Neurotransmitter Receptor Influence on Behavior via the 5-HT2A Receptor.
Abstract
Abstract Head-twitch behavior (HTR) is the behavioral signature of psychedelic drugs upon stimulation of the serotonin 5-HT 2A receptor (5-HT 2A R) in rodents. Following the previous report of a semi-automated detection of HTR based on the dynamics of mouse’s head movement, here we present a system for the identification of individual HTR events in a fully automated fashion. The validity of this fully automated HTR detection system was tested with the psychedelic drug DOI in 5-HT 2A R-KO mice, and via evaluation of potential sources of false-positive and false-negative HTR events. The increased throughput in data processing achieved via automation afforded the possibility of conducting otherwise time consuming HTR time-course studies. To further assess the versatility of our system, we also explored the pharmacological interactions between 5-HT 2A R and the metabotropic glutamate receptor 2 (mGluR2). Our data demonstrate the potentiation effect of the mGluR2/3 antagonist LY341495 on DOI-induced HTR, as well as the HTR-blocking effect of the mGluR2/3 agonist and antipsychotic drug in development LY404039. This fully automated system can contribute to speed up our understanding of 5-HT 2A R’s pharmacology and its characteristic behavioral outputs in rodents.