Altered Serotonin 2A (5-HT 2A ) Receptor Signaling Underlies Mild TBI-Elicited Deficits in Social Dominance.

Autor: Collins SM; Division of Pharmaceutical Sciences, University of Cincinnati James L. Winkle College of Pharmacy, Cincinnati, OH, United States., O'Connell CJ; Division of Pharmaceutical Sciences, University of Cincinnati James L. Winkle College of Pharmacy, Cincinnati, OH, United States., Reeder EL; Division of Pharmaceutical Sciences, University of Cincinnati James L. Winkle College of Pharmacy, Cincinnati, OH, United States., Norman SV; Department of Biological Sciences, University of Cincinnati College of Arts and Sciences, Cincinnati, OH, United States., Lungani K; Department of Biological Sciences, University of Cincinnati College of Arts and Sciences, Cincinnati, OH, United States., Gopalan P; Department of Biological Sciences, University of Cincinnati College of Arts and Sciences, Cincinnati, OH, United States., Gudelsky GA; Division of Pharmaceutical Sciences, University of Cincinnati James L. Winkle College of Pharmacy, Cincinnati, OH, United States.; Neuroscience Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH, United States., Robson MJ; Division of Pharmaceutical Sciences, University of Cincinnati James L. Winkle College of Pharmacy, Cincinnati, OH, United States.; Neuroscience Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
Jazyk: angličtina
Zdroj: Frontiers in pharmacology [Front Pharmacol] 2022 Jul 15; Vol. 13, pp. 930346. Date of Electronic Publication: 2022 Jul 15 (Print Publication: 2022).
DOI: 10.3389/fphar.2022.930346
Abstrakt: Various forms of traumatic brain injury (TBI) are a leading cause of disability in the United States, with the generation of neuropsychiatric complications such as depression, anxiety, social dysfunction, and suicidality being common comorbidities. Serotonin (5-HT) signaling is linked to psychiatric disorders; however, the effects of neurotrauma on normal, homeostatic 5-HT signaling within the central nervous system (CNS) have not been well characterized. We hypothesize that TBI alters specific components of 5-HT signaling within the CNS and that the elucidation of specific TBI-induced alterations in 5-HT signaling may identify novel targets for pharmacotherapies that ameliorate the neuropsychiatric complications of TBI. Herein, we provide evidence that closed-head blast-induced mild TBI (mTBI) results in selective alterations in cortical 5-HT 2A receptor signaling. We find that mTBI increases in vivo cortical 5-HT 2A receptor sensitivity and ex vivo radioligand binding at time points corresponding with mTBI-induced deficits in social behavior. In contrast, in vivo characterizations of 5-HT 1A receptor function revealed no effect of mTBI. Notably, we find that repeated pharmacologic activation of 5-HT 2A receptors post-injury reverses deficits in social dominance resulting from mTBI. Cumulatively, these studies provide evidence that mTBI drives alterations in cortical 5-HT 2A receptor function and that selective targeting of TBI-elicited alterations in 5-HT 2A receptor signaling may represent a promising avenue for the development of pharmacotherapies for TBI-induced generation of neuropsychiatric disorders.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Collins, O’Connell, Reeder, Norman, Lungani, Gopalan, Gudelsky and Robson.)
Databáze: MEDLINE
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