Fully automated head-twitch detection system for the study of 5-HT<sub>2A</sub> receptor pharmacology in vivo.
Abstract
Head-twitch behavior (HTR) is the behavioral signature of psychedelic drugs upon stimulation of the serotonin 5-HT<sub>2A</sub> receptor (5-HT<sub>2A</sub>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<sub>2A</sub>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<sub>2A</sub>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<sub>2A</sub>R's pharmacology and its characteristic behavioral outputs in rodents.
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