Neurochemical and Behavioral Profiling in Male and Female Rats of the Psychedelic Agent 25I-NBOMe.

Cristina Miliano,Nicholas Pintori,Maria Paola Castelli,Micaela Tirri,Maria Antonietta De Luca,Raffaella Arfè,Matteo Marti

doi:10.3389/fphar.2019.01406

Cristina Miliano, Nicholas Pintori + Show 5 more

Open Access

https://doi.org/10.3389/fphar.2019.01406

Copy DOI

Abstract

4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe), commonly called “N-Bomb,” is a synthetic phenethylamine with psychedelic and entactogenic effects; it was available on the Internet both as a legal alternative to lysergic acid diethylamide (LSD) and as a surrogate of 3,4-methylenedioxy-methamphetamine (MDMA), but now it has been scheduled among controlled substances. 25I-NBOMe acts as full agonist on serotonergic 5-HT2A receptors. Users are often unaware of ingesting fake LSD, and several cases of intoxication and fatalities have been reported. In humans, overdoses of “N-Bomb” can cause tachycardia, hypertension, seizures, and agitation. Preclinical studies have not yet widely investigated the rewarding properties and behavioral effects of this compound in both sexes. Therefore, by in vivo microdialysis, we evaluated the effects of 25I-NBOMe on dopaminergic (DA) and serotonergic (5-HT) transmissions in the nucleus accumbens (NAc) shell and core, and the medial prefrontal cortex (mPFC) of male and female rats. Moreover, we investigated the effect of 25I-NBOMe on sensorimotor modifications as well as body temperature, nociception, and startle/prepulse inhibition (PPI). We showed that administration of 25I-NBOMe affects DA transmission in the NAc shell in both sexes, although showing different patterns; moreover, this compound causes impaired visual responses in both sexes, whereas core temperature is heavily affected in females, and the highest dose tested exerts an analgesic effect prominent in male rats. Indeed, this drug is able to impair the startle amplitude with the same extent in both sexes and inhibits the PPI in male and female rats. Our study fills the gap of knowledge on the behavioral effects of 25I-NBOMe and the risks associated with its ingestion; it focuses the attention on sex differences that might be useful to understand the trend of consumption as well as to recognize and treat intoxication and overdose symptoms.

Highlights

The appearance of new psychoactive substances (NPS) is changing the trend in drug use worldwide (Orsolini et al, 2015; Miliano et al, 2016; UNODC, 2016; Corkery et al, 2017; Orsolini et al, 2017), which includes their safely perceived purchase on the Internet (Miliano et al, 2018)
The psychedelic compound 25I-NBOMe belongs to the phenethylamines that are a class of Novel psychoactive substances (NPS) spread among youth, with greater diffusion in girls than in boys (Wu et al, 2010; UNODC, 2016). 25I-NBOMe is a 5-HT2A receptor agonist used as a legal substitute of lysergic acid diethylamide (LSD) and to mimic the effect of methamphetamine as well (Le Roux et al, 2015; Palamar et al, 2016)
We have shown that the synthetic hallucinogen 25I-NBOMe affects the DArgic transmission in the nucleus accumbens (NAc) shell in a sex-independent manner, while medial prefrontal cortex (mPFC) DA seems to be more responsive in females compared to males

Summary

Introduction

The appearance of new psychoactive substances (NPS) is changing the trend in drug use worldwide (Orsolini et al, 2015; Miliano et al, 2016; UNODC, 2016; Corkery et al, 2017; Orsolini et al, 2017), which includes their safely perceived purchase on the Internet (Miliano et al, 2018). The N-benzylmethoxy derivatives of the 2C hallucinogens (i.e., 2C-I, 2C-B, and 2C-C), commonly called NBOMes (4-Iodo-2,5dimethoxy-N-(2-methoxybenzyl)phenethylamine), are probably the most famous; they used to be marketed as a legal lysergic acid diethylamide (LSD), with aliases such as “Smiles” and “N-bombs.” They act as full agonist on human and rat 5-HT2A receptors (Ki = 0.044 nM and Ki = 0.087 nM, respectively), with high affinity (Braden et al, 2006). Low doses of the order of 50 μg are able to produce psychoactive effects (Kyriakou et al, 2015; Suzuki et al, 2015) They are usually ingested sublingually, orally, by insufflations, rarely intravenously, and it seems to be active at doses as low as 50–250 μg, but the typical dose range is 500–800 μg (Halberstadt and Geyer, 2014). Several intoxication cases and some fatalities have been reported after the recreational use of 25-NBOMes

Objectives

Methods

Results

Discussion

Conclusion