The serotonin 1B receptor is required for some of the behavioral effects of psilocybin in mice
bioRxiv (Cold Spring Harbor Laboratory) October 21, 2024 Sixtine Fleury, Katherine M. Nautiyal 4 citations preprint
Psilocybin's persisting clinical effects are commonly attributed to activation of the serotonin 2A receptor, but its active metabolite binds to many serotonin receptor subtypes, including the serotonin 1B receptor (5-HT1BR). In mice, 5-HT1BR expression influenced brain-wide activity after psilocybin administration, measured by differences in c-Fos patterns across regions involved in emotional processing and cognitive function, including the amygdala and prefrontal cortex. 5-HT1BR mediated some acute and persisting behavioral effects: mice lacking 5-HT1BRs showed attenuated hypolocomotion to psilocybin, and both transgenic and pharmacological loss-of-function models indicated 5-HT1B involvement in decreased anhedonia and reduced anxiety-like behavior. The research implicates 5-HT1BR as a mediator of psilocybin's behavioral and neural effects in mice.