Fully automated head-twitch detection system for the study of 5-HT2A receptor pharmacology in vivo
Mario de la Fuente Revenga, Jong M. Shin, Hiba Vohra, Kelsey S. Hideshima, Matthew Schneck, Justin L. Poklis, Javier González-Maeso
Scientific Reports October 3, 2019 DOI: 10.1038/s41598-019-49913-4 via OpenAlex
Summary
AI-generated from the abstractA fully automated system detects head-twitch behavior (HTR) in mice, a behavioral marker of psychedelic drug action at the serotonin 5-HT2A receptor. The system was validated using the psychedelic DOI in mice lacking the 5-HT2A receptor and by evaluating false-positive and false-negative events. Automation enabled efficient time-course studies. Pharmacological interactions between the 5-HT2A receptor and metabotropic glutamate receptor 2 (mGluR2) were explored: the mGluR2/3 antagonist LY341495 potentiated DOI-induced HTR, while the mGluR2/3 agonist LY404039 blocked it. This system can accelerate understanding of 5-HT2A receptor pharmacology and its behavioral outputs in rodents.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | DOI LY341495 LY404039 |
| Keywords | Agonist Metabotropic glutamate receptor Metabotropic receptor Pharmacology Neuroscience |
| Citations | 57 |
| Key finding | The mGluR2/3 antagonist LY341495 potentiates DOI-induced head-twitch behavior, while the mGluR2/3 agonist LY404039 blocks it. |
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.