Mescaline-induced behavioral alterations are mediated by 5-HT2A and 5-HT2C receptors in rats.
Pharmacology, biochemistry, and behavior – December 01, 2024
Source: PubMed
Summary
Mescaline, a natural psychedelic, affects brain chemistry through specific serotonin receptors. New findings reveal how this compound influences behavior by targeting two key receptor types. When given to rats, mescaline altered both locomotor activity and sensorimotor gating. Blocking certain serotonin receptors prevented these changes, showing that mescaline's effects primarily work through 5-HT2A receptors, with secondary involvement of 5-HT2C receptors.
Abstract
Mescaline is a classical psychedelic compound with a phenylethylamine structure that primarily acts on serotonin 5-HT2A/C receptors, but also binds to 5-HT1A and 5-HT2B receptors. Despite being the first psychedelic ever isolated and synthesized, the precise role of different serotonin receptor subtypes in its behavioral pharmacology is not fully understood. In this study, we aimed to investigate how selective antagonists of 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT1A receptors affect the behavioral changes induced by subcutaneous administration of mescaline (at doses of 10, 20, and 100 mg/kg) in rats. We used adult male Wistar rats in all our experiments. We evaluated locomotor activity using the open field test, and assessed sensorimotor gating deficits by measuring prepulse inhibition (PPI) of acoustic startle reaction (ASR). While the highest dose of mescaline induced hyperlocomotion (p < 0.001), which almost all the other antagonists reversed (p < 0.05-0.001), the PPI deficits were selectively normalized by the 5-HT2A antagonist (p < 0.05-0.01). The 5-HT2C antagonist partially reversed the small PPI deficit induced by lower doses of mescaline (p = 0.0017). Our findings suggest that mescaline-induced changes in behavior are primarily mediated by the 5-HT2A receptor subtype, with less pronounced contributions from the 5-HT2C receptor. The other antagonists had limited effects.