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

The hallucinogen 25B-NBOMe produced rewarding and reinforcing effects in rats, as shown by conditioned place preference and self-administration tests. Blocking dopamine D1 or D2 receptors prevented these effects, while blocking serotonin 2A receptors did not. 25B-NBOMe increased dopamine levels and altered expression of dopamine-related proteins in brain reward regions. It also induced head twitch responses and altered delta and gamma brain wave activity, effects that were normalized by dopamine receptor antagonists. These findings suggest 25B-NBOMe has abuse potential mediated through the dopaminergic system.

Study at a glance

Abstract

Abstract An increasing number of N ‐2‐methoxybenzyl‐phenethylamine (NBOMe) derivatives are being misused worldwide, including the potent hallucinogen 2‐(4‐bromo‐2,5‐dimethoxyphenyl)‐ 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‐NBOMe‐mediated 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‐NBOMe‐induced 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 that 25B‐NBOMe may induce rewarding and reinforcing effects via a dopaminergic mechanism, suggesting its abuse potential.