A novel designer drug, 25N-NBOMe, exhibits abuse potential via the dopaminergic system in rodents

Seo, Jee-Yeon; Jang, Choon‐Gon; Kim, Kyungin; Lee, Boram; Kim, Young-Jung; Kim, Seon-Kyung; Kim, Seong-Eon; Lee, Yong-Sup; Kim, Hyoung‐Chun; Lee, Seok‐Yong; Jang, Choon‐Gon

doi:10.1016/j.brainresbull.2019.07.002

Cited by 23 publications

(30 citation statements)

References 51 publications

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“…All tested 25B‐NBOMe doses were also self‐administered by rats, although not in a dose‐dependent manner, indicating that 25B‐NBOMe may induce reinforcing effects. These findings are in line with a recent study, showing that 25N‐NBOMe , 31 a 5‐HT 2A receptor agonist and an analog of 25B‐NBOMe, elicits CPP and supports SA in rodents. Furthermore, our SA data show that 25B‐NBOMe has weaker reinforcing effects than METH, highlighting the pharmacological differences between the two substances.…”

Section: Discussionsupporting

confidence: 93%

25B‐NBOMe, a novel N‐2‐methoxybenzyl‐phenethylamine (NBOMe) derivative, may induce rewarding and reinforcing effects via a dopaminergic mechanism: Evidence of abuse potential

et al. 2019

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An increasing number of N-2-methoxybenzyl-phenethylamine (NBOMe) derivatives are being misused worldwide, including the potent hallucinogen 2-(4-bromo-2,5dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25B-NBOMe). However, the number of studies characterizing the abuse potential and psychopharmacological properties of 25B-NBOMe is limited; thus, we examined its rewarding and reinforcing effects using conditioned place preference (CPP) and self-administration (SA) tests. Pretreatment with SCH23390 (SCH), Haloperidol (HAL), and ketanserin (KS), antagonists of dopamine D1 (DRD 1), dopamine D2 (DRD 2), and serotonin 2A (5-HT 2A receptor) receptors, respectively, was utilized during a CPP test to investigate the involvement of the dopaminergic and serotonergic systems in 25B-NBOMemediated effects. We also examined the effects of 25B-NBOMe on the expression of dopamine-related proteins in the nucleus accumbens (NAcc) and ventral tegmental area (VTA). Then, we measured the dopamine level, phosphorylated CREB (p-CREB), deltaFosB (ΔFosB), and brain-derived neurotrophic factor (BDNF) in the NAcc. In addition, we explored the involvement of 5-HT 2A receptors in the 25B-NBOMeinduced head twitch response (HTR). We also examined the effects of 25B-NBOMe on brain wave activity using electroencephalography. 25B-NBOMe elicited CPP and SA. SCH and HAL blocked 25B-NBOMe-induced CPP, whereas KS did not. Moreover, 25B-NBOMe altered the DRD 1 , DRD 2 , and dopamine transporter expression and increased dopamine levels. It also induced changes in p-CREB, ΔFosB, and BDNF expression. 25B-NBOMe induced HTR and increased 5-HT 2A receptor mRNA levels, effects inhibited by KS. Furthermore, 25B-NBOMe altered delta and gamma wave activity, which was normalized by SCH and HAL. These findings show Raly James Perez Custodio and Leandro Val Sayson have contributed equally to this manuscript.

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Section: Discussionsupporting

confidence: 93%

25B‐NBOMe, a novel N‐2‐methoxybenzyl‐phenethylamine (NBOMe) derivative, may induce rewarding and reinforcing effects via a dopaminergic mechanism: Evidence of abuse potential

et al. 2019

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“…Therefore, they most likely have little or no pharmacological relevance to the actions of phenethylamine psychedelics. Rodent studies have suggested reinforcing effects for NBOMe derivatives that involve the dopaminergic system (Custodio et al 2019;Seo et al 2019). The NBOMe derivative 4-iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe) was shown to increase extracellular dopamine, 5-HT, and glutamate levels in the rat frontal cortex (Herian et al 2019), but unknown are the ways in which these findings translate to humans.…”

Section: Mechanism Of Action Of Phenethylaminesmentioning

confidence: 99%

Designer drugs: mechanism of action and adverse effects

2020

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Psychoactive substances with chemical structures or pharmacological profiles that are similar to traditional drugs of abuse continue to emerge on the recreational drug market. Internet vendors may at least temporarily sell these so-called designer drugs without adhering to legal statutes or facing legal consequences. Overall, the mechanism of action and adverse effects of designer drugs are similar to traditional drugs of abuse. Stimulants, such as amphetamines and cathinones, primarily interact with monoamine transporters and mostly induce sympathomimetic adverse effects. Agonism at l-opioid receptors and c-aminobutyric acid-A (GABA A) or GABA B receptors mediates the pharmacological effects of sedatives, which may induce cardiorespiratory depression. Dissociative designer drugs primarily act as N-methyl-D-aspartate receptor antagonists and pose similar health risks as the medically approved dissociative anesthetic ketamine. The cannabinoid type 1 (CB 1) receptor is thought to drive the psychoactive effects of synthetic cannabinoids, which are associated with a less desirable effect profile and more severe adverse effects compared with cannabis. Serotonergic 5-hydroxytryptamine-2A (5-HT 2A) receptors mediate alterations of perception and cognition that are induced by serotonergic psychedelics. Because of their novelty, designer drugs may remain undetected by routine drug screening, thus hampering evaluations of adverse effects. Intoxication reports suggest that several designer drugs are used concurrently, posing a high risk for severe adverse effects and even death.

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“…However, it has been shown that after repeated administration, other hallucinogens, such as LSD, DOM, and 25CN-NBOH, produce tolerance by downregulation of the 5-HT 2A receptor (Buchborn et al 2018;Buckholtz et al 1990;Gresch et al 2005). Furthermore, it has also been demonstrated that rewarding and reinforcing effects of 25I-NBOMe, 25B-NBOMe, and 25N-NBOMe on mice are related to the dopaminergic system, as changes in expression of dopamine D 1 and D 2 receptors, dopamine transporter DAT, tyrosine hydroxylase, and dopamine (DA) levels were found in the nucleus accumbens and ventral tegmental area (VTA) (Custodio et al 2019;Jeon et al 2019;Seo et al 2019).…”

Section: Introductionmentioning

confidence: 99%

Tolerance to neurochemical and behavioral effects of the hallucinogen 25I-NBOMe

et al. 2021

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Rationale 4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe) is a potent serotonin 5-HT2A/2C receptor agonist with hallucinogenic activity. There is no data on the 25I-NBOMe effect on brain neurotransmission and animal performance after chronic administration. Objectives We examined the effect of a 7-day treatment with 25I-NBOMe (0.3 mg/kg/day) on neurotransmitters’ release and rats’ behavior in comparison to acute dose. Methods Changes in dopamine (DA), serotonin (5-HT), acetylcholine (ACh), and glutamate release were studied using microdialysis in freely moving rats. The hallucinogenic activity was measured in the wet dog shake (WDS) test. The animal locomotion was examined in the open field (OF) test, short-term memory in the novel object recognition (NOR) test. The anxiogenic/anxiolytic properties of the drug were tested using the light/dark box (LDB) test. Results Repeated administration of 25I-NBOMe decreased the response to a challenge dose of DA, 5-HT, and glutamatergic neurons in the frontal cortex as well as weakened the hallucinogenic activity in comparison to acute dose. In contrast, striatal and accumbal DA and 5-HT release and accumbal but not striatal glutamate release in response to the challenge dose of 25I-NBOMe was increased in comparison to acute treatment. The ACh release was increased in all brain regions. Behavioral tests showed a motor activity reduction and memory deficiency in comparison to a single dose and induction of anxiety after the drug’s chronic and acute administration. Conclusions Our findings suggest that multiple injections of 25I-NBOMe induce tolerance to hallucinogenic activity and produce alterations in neurotransmission. 25I-NBOMe effect on short-term memory, locomotor function, and anxiety seems to be the result of complex interactions between neurotransmitter pathways.

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A novel designer drug, 25N-NBOMe, exhibits abuse potential via the dopaminergic system in rodents

Cited by 23 publications

References 51 publications

25B‐NBOMe, a novel N‐2‐methoxybenzyl‐phenethylamine (NBOMe) derivative, may induce rewarding and reinforcing effects via a dopaminergic mechanism: Evidence of abuse potential

25B‐NBOMe, a novel N‐2‐methoxybenzyl‐phenethylamine (NBOMe) derivative, may induce rewarding and reinforcing effects via a dopaminergic mechanism: Evidence of abuse potential

Designer drugs: mechanism of action and adverse effects

Tolerance to neurochemical and behavioral effects of the hallucinogen 25I-NBOMe

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