Abstract
NBOMes are N-benzylmethoxy derivatives of the 2C family hallucinogens. 4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe) is one of the commonly used illicit drugs. It exhibits high binding affinity for 5-HT2A/C and 5-HT1A serotonin receptors. Activation of 5-HT2A receptor induces head-twitch response (HTR) in rodents, a behavioral marker of hallucinogen effect in humans. There is not much data on neurochemical properties of NBOMes. Therefore, we aimed to investigate the effect of 25I-NBOMe on extracellular level of dopamine (DA), serotonin (5-HT), and glutamate (GLU) in the rat frontal cortex, tissue contents of monoamines, and hallucinogenic activity in rats. The extracellular levels of DA, 5-HT, and GLU were studied using microdialysis in freely moving animals. The tissue contents of DA, 5-HT and their metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were determined in the rat frontal cortex. We also tested a drug-elicited HTR. 25I-NBOMe at doses 1, 3, and 10 mg/kg (sc) increased extracellular DA, 5-HT, and GLU levels, enhanced tissue content of 5-HT and 5-HIAA, but did not affect tissue level of DA and its metabolites. The compound exhibited an inverted U-shaped dose-response curve with respect to the effect on extracellular DA and 5-HT levels, but a U-shaped dose-response curve was observed for its effect on GLU release and HTR. The data from our study suggest that hallucinogenic activity of 25I-NBOMe seems to be related with the increase in extracellular GLU level-mediated via cortical 5-HT2A receptors. The influence of 25I-NBOMe on 5-HT2C and 5-HT1A receptors may modulate its effect on neurotransmitters and HTR.
Highlights
New psychoactive substances (NPS) are substitutes of wellknown drugs with hallucinogenic effect on the central nervous system (CNS)
The obtained supernatants were filtered through 0.22 μm Ultrafree Centrifugal Filters (Merck Millipore Ltd., Ireland) and 3–5 μL of samples were injected into an high-performance liquid chromatography (HPLC) system
The changes in extracellular levels of DA, 5-HT, and glutamate in the rat frontal cortex may be explained by agonist activity of 25I-NBOMe at 5-HT2A receptors for which this drug has sub-nanomolar affinity (Rickli et al 2015). 5-HT2A receptors are highly expressed on glutamatergic pyramidal neurons and GABAergic basket and chandelier cells in layer V of the prefrontal cortex (Halberstadt 2015)
Summary
New psychoactive substances (NPS) are substitutes of wellknown drugs with hallucinogenic effect on the central nervous system (CNS). Hallucinogenic compounds have been known to mankind for centuries along with ethanol they might be one of the oldest known psychoactive substances (Nichols 2016; Schultes et al 1998). They produce a variety of effects after administration, mostly revolving around visual and auditory hallucinations and mental distortions (Nichols 2004; UNODC 2013) and their use leads to a rapid development of tolerance, and cross-tolerance phenomenon (Abramson et al 1956; Angrist et al 1974; Wolbach et al 1962). Indoleamines include ergolines, rigid structural analogues related to LSD, and simple tryptamines, such as DMT or 5-methoxy-DMT
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