title: A combined therapeutic regimen of buspirone and environmental enrichment is more efficacious than either alone in enhancing spatial learning in brain-injured pediatric rats.
abstract: Buspirone, a 5-HT1A receptor agonist, and environmental enrichment (EE) enhance cognition and reduce histopathology after traumatic brain injury (TBI) in adult rats, but have not been fully evaluated after pediatric TBI, which is the leading cause of death in children. Hence, the aims of this study were to assess the efficacy of buspirone alone (Experiment 1) and in combination with EE (Experiment 2) in TBI postnatal day-17 male rats. The hypothesis was that both therapies would confer cognitive and histological benefits when provided singly, but their combination would be more efficacious. Anesthetized rats received a cortical impact or sham injury and then were randomly assigned to receive intraperitoneal injections of buspirone (0.08 mg/kg, 0.1 mg/kg, and 0.3 mg/kg) or saline vehicle (1.0 mL/kg) 24 h after surgery and once daily for 16 days (Experiment 1). Spatial learning and memory were assessed using the Morris water maze (MWM) on post-operative days 11-16, and cortical lesion volume was quantified on day 17. Sham controls for each condition were significantly better than all TBI groups. In the TBI groups, buspirone (0.1 mg/kg) enhanced MWM performance versus vehicle and buspirone (0.08 mg/kg and 0.3 mg/kg) (p<0.05) and reduced lesion volume relative to vehicle (p=0.038). In Experiment 2, buspirone (0.1 mg/kg) or vehicle was combined with EE after TBI, and the data were compared to the standard (STD)-housed groups from Experiment 1. EE lead to a significant enhancement of spatial learning and a reduction in lesion size versus STD. Moreover, the combined treatment group (buspirone+EE) performed markedly better than the buspirone+STD and vehicle+EE groups, which suggests an additive effect and supports the hypothesis. The data replicate previous studies assessing these therapies in adult rats. These novel findings may have important rehabilitation-relevant implications for clinical pediatric TBI.
authors: 1 Physical Medicine & Rehabilitation, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors: Christina M
authors: CM
authors: Monaco
authors: Kory M
authors: KM
authors: Gebhardt
authors: Sarah M
authors: SM
authors: Chlebowski
authors: Kaitlyn E
authors: KE
authors: Shaw
authors: Jeffrey P
authors: JP
authors: Cheng
authors: Jeremy J
authors: JJ
authors: Henchir
authors: Margaret F
authors: MF
authors: Zupa
authors: Anthony E
authors: AE
authors: Kline
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy / Q000523:psychology / Q000534:rehabilitation*; D002065:Buspirone / Q000494:pharmacology* / Q000627:therapeutic use; D004777:Environment; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D017366:Serotonin Receptor Agonists; D002065:Buspirone
keywords: 5-HT1A receptor agonist, beam-walking; Morris water maze; behavior; controlled cortical impact (CCI); functional recovery; hippocampus; learning and memory; traumatic brain injury