Behavioural Brain Research
February 1, 2019
Arvie Abiero, Chrislean Jun Botanas, Leandro Val Sayson et al.
17 citations
5-MeO-AMT, a tryptamine used recreationally for its hallucinogenic and mood-elevating effects, triggers head-twitch response (HTR) in mice through activation of serotonin receptor 2a (5-HTR2a) in the prefrontal cortex. Acute administration at doses 0.3–10 mg/kg produced HTR, but repeated dosing led to tolerance. The 5-HTR2a antagonist ketanserin blocked the response. The drug increased 5-HTR2a mRNA and induced PKC-γ phosphorylation in the prefrontal cortex. 5-MeO-AMT did not produce locomotor sensitization, conditioned place preference, or self-administration, suggesting low abuse potential.
Archives of Toxicology
April 1, 2021
Young-Jung Kim, Shi-Xun Ma, Kwang-Hyun Hur et al.
10 citations
The drugs 2C-C and 2C-P, members of the 2C family of phenethylamines, show abuse potential and neurotoxic effects at high doses in animal models. In mice, both drugs produced conditioned place preference in a dose-dependent manner and increased self-administration in rats, indicating abuse potential. High doses decreased locomotor activity, rota-rod performance, and scores on memory tests (Y-maze, novel object recognition, passive avoidance). The drugs altered expression of D1 and D2 dopamine receptors, the dopamine transporter, and its phosphorylated form in the nucleus accumbens and medial prefrontal cortex, and increased c-Fos-positive cells in the nucleus accumbens. High doses also activated microglia, suggesting neuroinflammation in the striatum.
Archives of Pharmacal Research
April 1, 2024
Young-Jung Kim, Wun-A Kook, Shi-Xun Ma et al.
3 citations
25E-NBOMe, a novel psychoactive substance, induces conditioned place preference in male mice and self-administration in male rats, indicating abuse potential. The drug enhances dopamine transporter and dopamine D1 receptor expression in the nucleus accumbens, reduces dopamine levels, and activates intracellular signaling pathways. Blocking the D1 receptor or inhibiting D1 receptor-expressing neurons attenuates the conditioned place preference. The drug also produces hallucinogenic effects via serotonin 2A receptor activity, as shown by the head twitch response. These findings suggest that D1 receptor signaling may govern the addictive potential of 25E-NBOMe.
Biomolecules & Therapeutics
October 13, 2022
Shujie Wang, Anlin Zhu, Suresh Paudel et al.
3 citations
The serotonin 2A receptor (5-HT2AR) is involved in drug addiction and psychiatric disorders. This study examined how the chemical structures of phenethylamine and tryptamine derivatives affect their binding to 5-HT2AR. Phenethylamines showed higher binding affinity than tryptamines. For phenethylamines, adding alkyl or halogen groups at the para position of the phenyl ring improved binding, while oxygen-containing groups had mixed effects depending on their position. For tryptamines, oxygen-containing groups on the larger ring increased affinity, but alkyl groups on the smaller ring and ally groups on the nitrogen decreased it. Functional tests indicated that compounds with higher affinity also showed stronger activation of signaling pathways and receptor internalization, suggesting they act as agonists. These findings guide the design of new 5-HT2AR ligands for treating psychiatric disorders and drug abuse.
British Journal of Pharmacology
October 1, 2021
Kwang-Hyun Hur, Seong-Eon Kim, Shi-Xun Ma et al.
Methoxphenidine, a dissociative designer drug, produces addictive behaviors in rats and mice through reinforcing and rewarding effects, activating dopamine pathways in the nucleus accumbens. It also induces schizophrenia-related symptoms—positive (hyperactivity, impulsivity), negative (anxiety, social withdrawal, depression), and cognitive impairment—by disrupting the hippocampal-prefrontal cortex pathway, a circuit implicated in schizophrenia. These findings support legal restrictions on recreational use and suggest methoxphenidine may serve as a tool for developing animal models of addiction and schizophrenia.
Brain Research Bulletin
March 1, 2018
The-Vinh Tran, Se Jin Park, Eun-Joo Shin et al.
Repeated treatment of mice with phencyclidine (PCP), a drug that induces schizophrenia-like symptoms, increased expression of the platelet-activating factor receptor (PAF-R) in the prefrontal cortex and hippocampus, with a greater increase in the prefrontal cortex. This was accompanied by increased activity of the proinflammatory molecule nuclear factor kappa B (NF-κB). Blocking PAF-R with the antagonist ginkgolide B, using PAF-R knockout mice, or inhibiting NF-κB with pyrrolidine dithiocarbamate each reduced PCP-induced abnormal behaviors including reduced sociability, depression, cognitive impairment, and behavioral sensitization. The findings suggest PAF-R drives PCP-induced neuropsychotoxicity through an NF-κB-dependent mechanism and may be linked to schizophrenia-like behavior.
Journal of medicinal food
October 1, 2016
The-Vinh Tran, Eun-Joo Shin, Sung Kwon Ko et al.
Mountain-cultivated ginseng (MG) reduces schizophrenia-like behaviors in mice treated with phencyclidine (PCP) by positively modulating the glutathione system. PCP caused abnormal behaviors, decreased the ratio of reduced to oxidized glutathione (GSH/GSSG), and reduced glutathione peroxidase (GPx) activity in the prefrontal cortex, while increasing Nrf2 activity and glutamate-cysteine ligase (GCL) expression. MG (200 mg/kg) given for seven days after PCP treatment reversed these behavioral and biochemical changes, with effects comparable to the antipsychotic clozapine. The findings suggest MG protects against PCP-induced psychosis through restoring glutathione system function.