Acute Effects of the Psychedelic Phenethylamine 25I-NBOMe in C57BL/6J Male Mice.

The synthetic psychedelic 25I-NBOMe, a selective 5HT2A receptor agonist abused as a counterfeit LSD, alters dopamine transmission, behavior, and synaptic plasticity in mice. At the highest dose tested (1 mg/kg), it increased dopamine levels in the nucleus accumbens shell. It also increased reaction time within 30 minutes after administration and disrupted prepulse inhibition, indicating sensorimotor gating deficits. In brain slices, 25I-NBOMe prevented long-term potentiation in the medial prefrontal cortex, an effect not reversed by a selective 5HT2A antagonist. These findings highlight risks of 25I-NBOMe use, including altered neurotransmission and impaired cognitive processes.

Study at a glance

Abstract

25I-NBOMe (4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl) phenethylamine) is a synthetic psychedelic compound abused for its ambiguous legal state as a counterfeit lysergic acid diethylamide (LSD). 25I-NBOMe acts as a selective agonist of 5HT2A receptors leading to hallucinations, intoxications, and fatalities. Here, we assessed the rewarding properties of 25I-NBOMe and its behavioral and neurotoxic acute effects on the central nervous system of C57BL/6J mice. We evaluated the dopamine (DA) levels using in vivo microdialysis in the nucleus accumbens (NAc) shell after 25I-NBOMe (0.1-1 mg/kg i.p.) injection. We also investigated the effects of 25I-NBOMe (0.1-1 mg/kg i.p.) on locomotor activity, reaction time, and prepulse inhibition. Moreover, we assessed the acute 25I-NBOMe (1 µM) effects on synaptic transmission and plasticity in the medial prefrontal cortex (mPFC) by using ex vivo electrophysiology. Our findings suggest that 25I-NBOMe affects the DA transmission in NAc shell at the highest dose tested, increases the reaction time within 30 min after the administration, and disrupts the PPI. In slices, it prevents long-term synaptic potentiation (LTP) in the mPFC, an effect that could not be reverted by the co-administration of the selective 5HT2A antagonist (MDL100907). Overall, these findings provide valuable new insights into the effects of 25I-NBOMe and the associated risks of its use.