Neurochemical and Behavioral Effects of a New Hallucinogenic Compound 25B-NBOMe in Rats

Adam Wojtas,Karolina Noworyta-Sokołowska,Krystyna Gołembiowska,Mateusz Skawski,Monika Herian,Małgorzata Sobocińska,Alejandro González-Marín

doi:10.1007/s12640-020-00297-8

Adam Wojtas, Karolina Noworyta-Sokołowska + Show 5 more

Open Access

https://doi.org/10.1007/s12640-020-00297-8

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Abstract

4-Bromo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25B-NBOMe) is a hallucinogen exhibiting high binding affinity for 5-HT2A/C serotonin receptors. In the present work, we investigated its effect on dopamine (DA), serotonin (5-HT), acetylcholine (ACh), and glutamate release in the rat frontal cortex, striatum, and nucleus accumbens. Hallucinogenic activity, impact on cognitive and motor functions, and anxiogenic/anxiolytic properties of this compound were also tested. The release of DA, 5-HT, ACh, and glutamate was studied using microdialysis in freely moving animals. Hallucinogenic activity was investigated using head and body twitch response (WDS), cognitive functions were examined with the novel object recognition test (NOR), locomotor activity was studied in the open field (OF), while anxiogenic/anxiolytic effect was tested using the light/dark box (LDB). Neurotoxicity was evaluated with the comet assay. 25B-NBOMe increased DA, 5-HT, and glutamate release in all studied brain regions, induced hallucinogenic activity, and lowered the recognition index (Ri) vs. control in the NOR test. It also decreased locomotor activity of rats in the OF test. The effect of 25B-NBOMe in the NOR test was inhibited by scopolamine. In the LDB test, the time spent in the dark zone was longer in comparison to control and was dose-dependent. In contrast to MDMA, 25B-NBOMe showed subtle genotoxic effect observed in the comet assay.Our findings indicate that 25B-NBOMe shows hallucinogenic activity in the wide range of doses. The changes in neurotransmitter levels may be related to 25B-NBOMe affinity for 5-HT2A receptor. Alterations in the NOR, OF, and LDB indicate that 25B-NBOMe impacts short-term memory, locomotion, and may be anxiogenic.

Highlights

It is without a doubt that humans have been using hallucinogens for ages; along with ethanol, they are the oldest psychoactive substances known to mankind (Nichols 2016; Schultes et al 2001)
All hallucinogens produce head twitch response (HTR) in rodents, a phenomenon that is parallel to hallucinations in humans, as this effect can be a factor differentiating hallucinogenic from non-hallucinogenic 5-HT2A receptor agonists (González-Maeso et al 2007; Halberstadt and Geyer 2013)
We have demonstrated that another NBOMe compound, 25I-NBOMe, having similar in vitro affinity for 5-HT2A receptor, affected DA, serotonin (5-HT), and glutamatergic neurotransmission and showed hallucinogenic activity (Herian et al 2019)

Summary

Introduction

It is without a doubt that humans have been using hallucinogens for ages; along with ethanol, they are the oldest psychoactive substances known to mankind (Nichols 2016; Schultes et al 2001). Classical hallucinogens can be divided by their structure into 2 main categories: indoleamines, e.g., DMT (N,Ndimethyltryptamine) or LSD (lysergic acid diethylamide), and phenylalkylamines, e.g., mescaline or DOI (2,5-dimethoxy-4-iodoamphetamine) (Nichols 2012). While the former demonstrate affinity for most subgroups of 5-HT receptors, the latter bind mainly to the 5-HT2 receptor family (Pierce and Peroutka 1989; Titeler et al 1988).

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