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.
Journal of Psychopharmacology
July 10, 2020
Raly James Perez Custodio, Leandro Val Sayson, Chrislean Jun Botanas et al.
15 citations
The substituted phenethylamines MAL and BOD have different abuse potentials. MAL produced psychostimulant effects, locomotor sensitization, and was self-administered by rats, indicating reinforcing properties. Both drugs induced conditioned place preference in mice, which was blocked by dopamine receptor antagonists, and both altered dopamine receptor D1 and D2 protein expression in the nucleus accumbens, tyrosine hydroxylase and dopamine transporter in the ventral tegmental area, increased dopamine levels in the nucleus accumbens, and enhanced delta and gamma brain wave activity. BOD caused locomotor depression and lacked rewarding and reinforcing effects, suggesting little to no capability to engender compulsive behavior despite its dopaminergic alterations.
Neuropharmacology
August 1, 2021
Chrislean Jun Botanas, Raly James Perez Custodio, Hee Jin Kim et al.
13 citations
Both enantiomers of methoxetamine (MXE), a ketamine analog, produce rapid antidepressant effects in mice, but the R-enantiomer causes fewer behavioral side effects. S-MXE and R-MXE both bind to NMDA receptors and inhibit serotonin transporters. At 10 mg/kg, each enantiomer reduced depression-like behavior and increased gamma brain waves, effects blocked by an AMPA receptor antagonist. They also boosted mTOR signaling and AMPA receptor subunit proteins in the hippocampus or prefrontal cortex, and increased serotonin receptor mRNA levels; a serotonin receptor antagonist blocked their antidepressant effects. Unlike S-MXE, R-MXE did not cause prepulse inhibition deficits, hyperactivity, conditioned place preference, or locomotor sensitization, though it briefly impaired motor coordination. R-MXE may be a safer antidepressant candidate.
Psychopharmacology
July 1, 2025
Raly James Perez Custodio, Darlene Mae Ortiz, Hyun Jun Lee et al.
8 citations
The psychedelic effects of serotonergic compounds are thought to rely primarily on activating 5-HT2A receptors, but this study in male mice shows that the 5-HT2C receptor can also independently induce the head-twitch response, a behavioral marker of psychedelic activity. The compounds Methallylescaline (MAL) and 4-Methyl-2,5,β-trimethoxyphenethylamine (BOD) produced head-twitch responses at 1 mg·kg⁻¹ through both 5-HT2A and 5-HT2C receptors, with distinct signaling pathways. At a higher dose of 30 mg·kg⁻¹, these compounds also triggered neurotoxic effects and activated pro-inflammatory cytokines, indicating potential harm beyond their psychedelic actions.
Frontiers in Pharmacology
March 16, 2023
Leandro Val Sayson, Darlene Mae Ortiz, Hyun Jun Lee et al.
4 citations
Mice lacking the Cryab gene show stronger addiction-like responses to the synthetic cannabinoid JWH-018, including greater self-administration and place preference, along with altered gamma brain waves, compared to normal mice. Repeated JWH-018 exposure did not change endocannabinoid or dopamine gene expression or dopamine levels in the brain's reward center between the two groups. However, the knockout mice displayed increased neuroinflammation, linked to upregulated NF-κB, and higher levels of synaptic plasticity markers. These findings suggest that heightened neuroinflammation via NF-κB may drive the enhanced cannabinoid addiction-related behaviors in Cryab knockout mice, making them a potential model for studying susceptibility to cannabinoid abuse.
Biomolecules & Therapeutics
February 15, 2023
Darlene Mae Ortiz, Mikyung Kim, Hyun Jun Lee et al.
3 citations
A novel compound called 4-F-PCP, structurally similar to ketamine and an NMDA receptor antagonist, shows antidepressant-like effects in mice. Doses of 3 and 10 mg/kg produced rapid and sustained effects, and repeated treatments remained effective. The compound reversed depression-related changes in synaptic plasticity proteins and altered excitatory amino acid transporters. At a 3 mg/kg dose, 4-F-PCP did not impair cognitive function in mice after up to 21 days of treatment. These findings suggest that 4-F-PCP may offer a faster-acting antidepressant with fewer side effects, though further research is needed.
International journal of molecular sciences
June 29, 2020
In Soo Ryu, Oc-Hee Kim, Young Eun Lee et al.
The designer drug 4'-F-PCP, a derivative of the dissociative anesthetic phencyclidine (PCP), shows a high potential for abuse. In rodents, a 10 mg/kg dose increased movement and rearing, and produced conditioned place preference, indicating rewarding effects. Intravenous self-administration of 1.0 mg/kg/infusion was robust, with a higher breakpoint under progressive ratio schedules, suggesting strong reinforcing properties. The drug altered dopamine transporter and D1 receptor expression in the nucleus accumbens and increased phosphorylated ERK, CREB, c-Fos, and FosB/ΔFosB, indicating activation of dopamine-related signaling pathways. These findings indicate that 4'-F-PCP has significant abuse liability.
Psychopharmacology
March 1, 2020
Arvie Abiero, Chrislean Jun Botanas, Raly James Custodio et al.
Two synthetic dissociative drugs, 4-MeO-PCP and 3-MeO-PCMo, produce rewarding and reinforcing effects in rats, indicating potential for abuse in humans. Both drugs induced conditioned place preference and self-administration, but only 4-MeO-PCP caused locomotor sensitization. Blocking dopamine D1 or D2 receptors prevented the drugs' rewarding effects. The drugs altered dopamine-related proteins and increased delta and gamma brain wave activity, effects also blocked by dopamine antagonists. These findings suggest the drugs' abuse potential is mediated through the mesolimbic dopamine system.