Tolerance and Tachyphylaxis to Head Twitches Induced by the 5-HT2A Agonist 25CN-NBOH in Mice

Frontiers in Pharmacology
Tobias BuchbornThomas Knöpfel

Abstract

The serotonin (5-HT) 2A receptor is the primary molecular target of serotonergic hallucinogens, which trigger large-scale perturbations of the cortex. Our understanding of how 5-HT2Aactivation may cause the effects of hallucinogens has been hampered by the receptor unselectivity of most of the drugs of this class. Here we used 25CN-NBOH (N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine), a newly developed selective 5-HT2Aagonist, and tested it with regard to the head-twitch-response (HTR) model of 5-HT2Aactivity and effects on locomotion. 25CN-NBOH evoked HTRs with an inverted u-shape-like dose-response curve and highest efficacy at 1.5 mg/kg, i.p. HTR occurrence peaked within 5 min after agonist injection, and exponentially decreased to half-maximal frequency at ~11 min. Thorough habituation to the experimental procedures (including handling, saline injection, and exposure to the observational boxes 1 day before the experiment) facilitated the animals' response to 25CN-NBOH. 25CN-NBOH (1.5 mg/kg, i.p.) induced HTRs were blocked by the 5-HT2Aantagonist ketanserin (0.75 mg/kg, 30 min pre), but not by the 5-HT2Cantagonist SB-242084 (0.5 mg/kg, i.p., 30 min pre). SB-242084 instead slightly increased the number of HTRs occ...Continue Reading

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Citations

Oct 5, 2019·Scientific Reports·Mario de la Fuente RevengaJavier González-Maeso
May 13, 2020·Expert Opinion on Investigational Drugs·Kirsten Antonio-Tolentino, Corey R Hopkins
Oct 24, 2020·Neurochemical Research·Anton S TsybkoVladimir S Naumenko
Nov 25, 2020·Molecular Biology Reports·Alec J DiVito, Robert F Leger
Feb 18, 2021·Behavioural Pharmacology·Anna U OdlandJesper T Andreasen
Mar 28, 2020·ACS Chemical Neuroscience·Emil Marcher-RørstedJesper L Kristensen
Oct 29, 2019·ACS Chemical Neuroscience·Christian B M PoulieJesper L Kristensen

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