Hallucinogenic activity, neurotransmitters release, anxiolytic and neurotoxic effects in Rat's brain following repeated administration of novel psychoactive compound 25B-NBOMe

Adam Wojtas; Monika Herian; Marzena Maćkowiak; Anna Solarz; Agnieszka Wawrzczak-Bargiela; Agnieszka Bysiek; Karolina Noworyta; Krystyna Gołembiowska

doi:10.1016/j.neuropharm.2023.109713

Hallucinogenic activity, neurotransmitters release, anxiolytic and neurotoxic effects in Rat's brain following repeated administration of novel psychoactive compound 25B-NBOMe

Neuropharmacology. 2023 Dec 1:240:109713. doi: 10.1016/j.neuropharm.2023.109713. Epub 2023 Sep 9.

Authors

Adam Wojtas¹, Monika Herian¹, Marzena Maćkowiak², Anna Solarz², Agnieszka Wawrzczak-Bargiela², Agnieszka Bysiek¹, Karolina Noworyta¹, Krystyna Gołembiowska³

Affiliations

¹ Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Pharmacology, 31-343, Kraków, 12 Smętna, Poland.
² Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Pharmacology, Laboratory of Pharmacology and Brain Biostructure, 31-343, Kraków, 12 Smętna, Poland.
³ Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Pharmacology, 31-343, Kraków, 12 Smętna, Poland. Electronic address: nfgolemb@cyf-kr.edu.pl.

PMID: 37689261
DOI: 10.1016/j.neuropharm.2023.109713

Abstract

2-(4-Bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)etanoamine (25B-NBOMe) is a highly selective 5-HT_2A receptor agonist, exhibiting a potent hallucinogenic activity. In the present study, we investigated the effect of a 7-day treatment with 25B-NBOMe in a dose of 0.3 mg/kg on the following: the neurotransmitter release in vivo using microdialysis in freely moving animals, hallucinogenic activity measured in the Wet Dog Shake (WDS) test, anxiety level as measured in the light/dark box (LDB) and locomotor activity in the open field (OF) test, DNA damage with the comet assay, and on a number of neuronal and glial cells with immunohistochemistry. Repeated administration of 25B-NBOMe decreased the response to a challenge dose (0.3 mg/kg) on DA, 5-HT and glutamatergic neurons in the rats' frontal cortex, striatum, and nucleus accumbens. The WDS response dropped drastically after the second day of treatment, suggesting a rapid development of tolerance. LDB and OF tests showed that the effect of 25B-NBOMe on anxiety depends on the treatment and environmental settings. Results obtained with the comet assay indicate a genotoxic properties in the frontal cortex and hippocampus. An increase in immunopositive glial but not neuronal cells was observed in the cortical regions but not in the hippocampus. In conclusion, our study showed that a chronic administration of 25B-NBOMe produces the development of tolerance observed in the neurotransmitters release and hallucinogenic activity. The oxidative damage of cortical and hippocampal DNA implies the generation of free radicals by the drug, resulting in genotoxicity but rather not in neurotoxic tissue damage. Behavioral tests show that 25B-NBOMe exerts anxiogenic effect after single and repeated treatment.

Keywords: 25B-NBOMe; Anxiety; Cell number; Genotoxicity; Hallucinogenic activity; Neurotransmitter release.