Characterization of the head-twitch response induced by hallucinogens in mice

Abstract

Rationale The head-twitch response (HTR) is a rapid side-to-side rotational head movement that occurs in rats and mice after administration of serotonergic hallucinogens and other 5-HT2A agonists. The HTR is widely used as a behavioral assay for 5-HT2A activation and to probe for interactions between the 5-HT2A receptor and other transmitter systems. Objective High-speed video recordings were used to analyze the head movement that occurs during head twitches in C57BL/6J mice. Experiments were also conducted in C57BL/6J mice to determine whether a head-mounted magnet and a magnetometer coil could be used to detect the HTR induced by serotonergic hallucinations based on the dynamics of the response. Results Head movement during the HTR was highly rhythmic and occurred within a specific frequency range (mean reciprocation frequency of 90.3 Hz). Head twitches produced wave-like oscillations of magnetometer coil voltage that matched the frequency of head movement during the response. The magnetometer coil detected the HTR induced by the serotonergic hallucinogens 2,5-dimethoxy-4-iodoamphetamine (DOI; 0.25, 0.5, and 1.0 mg/kg, IP) and lysergic acid diethylamide (LSD; 0.05, 0.1, 0.2, and 0.4 mg/kg, IP) with extremely high sensitivity and specificity. Magnetometer coil recordings demonstrated that the non-hallucinogenic compounds (+)-amphetamine (2.5 and 5.0 mg/kg, IP) and lisuride (0.8, 1.6, and 3.2 mg/kg, IP) did not induce the HTR. Conclusions These studies confirm that a magnetometer coil can be used to detect the HTR induced by hallucinogens. The use of magnetometer-based HTR detection provides a high-throughput, semi-automated assay for this behavior, and offers several advantages over traditional assessment methods.

Psychedelics

“…Although it has most often been visually scored in real time, or scored from videos taken during the drug effect, Halberstadt and Geyer (2013a) recently developed an automated and relatively rapid method for assessing the mouse HTR. They first analyzed the kinematics of head twitches using high-speed video recordings, reporting that the HTR was highly rhythmic, occurring within a specific frequency range (mean head movement frequency of 90.3 Hz).…”

“…This advancement allows the HTR to be used as a fairly rapid high-throughput assay that has eliminated the need for tedious visual scoring by an observer, and it gives reliable, unbiased, and reproducible results. Use of the mouse HTR to study psychedelics has recently been reviewed (Fantegrossi et al, 2008a;Canal and Morgan, 2012;Halberstadt and Geyer, 2013a;Hanks and González-Maeso, 2013).…”

GLYX-13 Produces Rapid Antidepressant Responses with Key Synaptic and Behavioral Effects Distinct from Ketamine

“…To examine this possibility, we assessed behavioral response to a 5-HT 2A/C receptor agonist DOI that increases head twitches in mice (Halberstadt and Geyer, 2013;Willins and Meltzer, 1997). Mice were administered ketamine or GLYX-13 and the levels of DOI-induced head twitches were determined 24 hr later.…”

“…Head twitch responses were assessed according to published methods (Halberstadt and Geyer, 2013). C57Bl/6 mice were habituated to testing chambers for 30 min and 24 hr later they received acute doses of either ketamine (10 mg/kg, i.v.)…”

Next generation of novel psychoactive substances on the horizon – A complex problem to face

“…However, unlike LSD, NBOMe drugs exert significant sympathomimetic activity and can lead to acute toxicity (see below). Mild hallucinogenic effects of 25C-NBOMe and 25I-NBOMe taken sublingually or intranasally can be achieved at doses as low as 50-200 g, strong after 350-800 g, and very strong over 700-800 g Halberstadt and Geyer, 2013;Nikolaou et al, 2015;Zuba et al, 2013). The drugs are only slightly less potent than LSD, which is usually taken in doses 25-250 μg.…”