Transient Elevation of Plasma Glucocorticoids Supports Psilocybin-Induced Anxiolysis in Mice.

Autor: Jones NT; Molecular and Cellular Pharmacology Training Program, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States., Zahid Z; Neuroscience Training Program, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States., Grady SM; Department of Anesthesiology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States., Sultan ZW; Department of Anesthesiology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States., Zheng Z; School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States., Razidlo J; Neuroscience Training Program, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States., Banks MI; Neuroscience Training Program, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.; Department of Anesthesiology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.; Transdisciplinary Center for Research in Psychoactive Substances, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States., Wenthur CJ; Molecular and Cellular Pharmacology Training Program, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.; Neuroscience Training Program, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.; School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.; Transdisciplinary Center for Research in Psychoactive Substances, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
Jazyk: angličtina
Zdroj: ACS pharmacology & translational science [ACS Pharmacol Transl Sci] 2023 Aug 02; Vol. 6 (8), pp. 1221-1231. Date of Electronic Publication: 2023 Aug 02 (Print Publication: 2023).
DOI: 10.1021/acsptsci.3c00123
Abstrakt: While correlations between drug-induced cortisol elevation, self-reported anxiety, and treatment outcomes have been reported for human studies during psilocybin-assisted psychotherapy, the mechanistic relationship between psychedelic-associated alterations in plasma glucocorticoid responses and the time course of anxious responsiveness remains unclear. Using rodents, both time-bound manipulation of glucocorticoid concentrations and assessment of anxiety-like behaviors can be achieved. Here, 3 mg/kg IP psilocybin was found to have anxiolytic-like effects in C57BL/6 male mice at 4 h after treatment. These effects were not altered by pretreatment with a 5-HT 2A antagonist but were blunted by pretreatment with a glucocorticoid receptor antagonist or suppression of psilocybin-induced corticosterone elevations. Anxiolytic-like effects were also observed at 4 h following treatment with the nonpsychedelic 5-HT 2A agonist lisuride at a dose causing a similar increase in plasma glucocorticoids as that seen with psilocybin, as well as following stress-induced (via repeated injection) glucocorticoid release alone. Psilocybin's anxiolytic-like effects persisted at 7 days following administration. The long-term anxiolytic effects of psilocybin were lost when psilocybin was administered to animals with ongoing chronic elevations in plasma corticosterone concentrations. Overall, these experiments indicate that acute, resolvable psilocybin-induced glucocorticoid release drives the postacute anxiolytic-like effects of psilocybin in mice and that its long-term anxiolytic-like effects can be abolished in the presence of chronically elevated plasma glucocorticoid elevations.
Competing Interests: The authors declare no competing financial interest.
(© 2023 The Authors. Published by American Chemical Society.)
Databáze: MEDLINE
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