2019/11/20 by Raly James Perez Custodio, Leandro Val Sayson, Chrislean Jun Botanas +11 · 1 citation
Neuroscience · #Neurotransmitter Receptor Influence on Behavior #Neuroscience and Neuropharmacology Research #Tryptophan and brain disorders
paper · doi:10.1111/adb.12850
openalex publication_date 2019/11/20 · openalex created_date 2019/12/05 · openalex updated_date 2026/07/30
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.