Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada. Electronic address: paul.fletcher@camh.ca.
2 papers in the library · 11 citations · publishing 2023-2024
Psilocybin, a 5-HT2A receptor agonist and hallucinogen, is being investigated as a treatment for neuropsychiatric disorders like depression, which involve attention deficits. In a rodent continuous performance task (CPT), psilocybin (0.3, 1, and 3 mg/kg), the 5-HT2A agonist TCB-2, and the antagonist M100907 all reduced hit and false alarm rates and induced conservative responding. Psilocybin also reduced target discrimination. These effects occurred primarily at doses that also reduced locomotor activity. No drug effects were seen on a more difficult CPT or after repeated psilocybin injections. The results provide little support for psilocybin altering visual attention or for 5-HT2A receptors modulating this process.
Psychedelic drugs that activate the 5-HT2A receptor, such as psilocybin, show promise for treating alcohol-use disorders. This study tested whether psilocybin or the 5-HT2A agonist TCB-2 could reverse the sensitized locomotor activity caused by repeated ethanol exposure in male DBA/2J mice. Mice received repeated ethanol injections to induce sensitization, then five daily doses of psilocybin (0, 0.3, or 1 mg/kg) or TCB-2 (0, 1, or 3 mg/kg). A subsequent ethanol challenge showed that sensitized mice still had enhanced activity, and neither psilocybin nor TCB-2 reduced this sensitized response. The results suggest that these drugs' short-term effects on ethanol intake may not involve reversing long-term behavioral or neural adaptations from repeated ethanol exposure.