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.
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.
Psychopharmacology
March 19, 2019
L. Sayson, Chrislean Jun Botanas, Raly James Perez Custodio et al.
Three novel analogs of methoxetamine (MXE), an NMDA receptor antagonist related to ketamine, showed antidepressant-like effects in mice. The compounds—NENK, 2-MeO-NEK, and 4-MeO-NEK—reduced immobility time in the forced swimming and tail suspension tests, indicating reduced behavioral despair. Their effects were blocked by an AMPA receptor antagonist (NBQX) and a 5-HT2 receptor antagonist (ketanserin), suggesting involvement of both glutamatergic and serotonergic systems. The analogs also altered mRNA levels of AMPA receptor subunits and brain-derived neurotrophic factor in the hippocampus and prefrontal cortex. These findings suggest the compounds may offer rapid antidepressant effects, though further research is needed.