%0 Journal Article
%T Gs signaling pathway distinguishes hallucinogenic and nonhallucinogenic 5-HT2AR agonists induced head twitch response in mice.
%A Liu X
%A Zhu H
%A Gao H
%A Tian X
%A Tan B
%A Su R
%J Biochem Biophys Res Commun
%V 598
%N 0
%D 04 2022 2
%M 35149433
%F 3.322
%R 10.1016/j.bbrc.2022.01.113
%X 5- HT2A receptor is a member of the family A G-protein-coupled receptor. It is involved in many psychiatric disorders, such as depression, addiction and Parkinson's disease. 5-HT2AR targeted drugs play an important role in regulating cognition, memory, emotion and other physiological function by coupling G proteins, and their most notable function is stimulating the serotonergic hallucination. However, not all 5-HT2AR agonists exhibit hallucinogenic activity, such as lisuride. Molecular mechanisms of these different effects are not well illustrated. This study suggested that 5-HT2AR coupled both Gs and Gq protein under hallucinogenic agonists DOM and 25CN-NBOH stimulation, but nonhallucinogenic agonist lisuride and TBG only activates Gq signaling. Moreover, in head twitch response (HTR) model, we found that cAMP analogs 8-Bromo-cAMP and PDE4 inhibitor Rolipram could increase HTR, while Gs protein inhibitor Melittin could reduce HTR. Collectively, these results revealed that Gs signaling is a key signaling pathway that may distinguish hallucinogenic agonists and nonhallucinogenic agonists.