title: 5-hydroxytryptamine1A (5-HT1A) receptor agonists: A decade of empirical evidence supports their use as an efficacious therapeutic strategy for brain trauma.
abstract: Traumatic brain injury (TBI) is a significant and enduring health care issue with limited treatment options. While several pre-clinical therapeutic approaches have led to enhanced motor and/or cognitive performance, the benefits of these treatments have not translated to the clinic. One plausible explanation is that the therapies may not have been rigorously evaluated, thus rendering the bench-to-bedside leap premature and subsequently unsuccessful. An approach that has undergone considerable empirical research after TBI is pharmacological targeting of 5-HT1A receptors with agonists such as repinotan HCl, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), and buspirone. The goal of this review is to integrate and interpret the findings from a series of studies that evaluated the efficacy of 5-HT1A receptor agonists on functional, histological, and molecular outcome after acquired brain injury. The overwhelming consensus of this exhaustive review is that a decade of empirical evidence supports their use as an efficacious therapeutic strategy for brain trauma. This article is part of a Special Issue entitled SI:Brain injury and recovery.
authors.affiliation: Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA 15213, United States; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA 15213, United States.
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Cheng
authors.affiliation: Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA 15213, United States; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA 15213, United States.
authors.forename: Jacob B
authors.initials: JB
authors.lastname: Leary
authors.affiliation: Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA 15213, United States.
authors.forename: Aerin
authors.initials: A
authors.lastname: Sembhi
authors.affiliation: Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA 15213, United States; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA 15213, United States.
authors.forename: Clarice M
authors.initials: CM
authors.lastname: Edwards
authors.affiliation: Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA 15213, United States; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA 15213, United States; Center for Neuroscience, University of Pittsburgh 1letab, Pittsburgh, PA 15213, United States.
authors.forename: Corina O
authors.initials: CO
authors.lastname: Bondi
authors.affiliation: Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA 15213, United States; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA 15213, United States; Psychology, University of Pittsburgh, Pittsburgh, PA 15213, United States; Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA 15213, United States; Center for Neuroscience, University of Pittsburgh 1letab, Pittsburgh, PA 15213, United States; Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA 15213, United States. Electronic address: klineae@upmc.edu.
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Kline
mesh_terms: D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents; D058825:Serotonin 5-HT1 Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A
keywords: 5-HT(1A) receptor agonists; Behavioral outcome; Controlled cortical impact; Functional recovery; Hippocampus; Learning and memory; Morris water maze; Serotonin(1A); Traumatic brain injury