title: The Therapeutic Efficacy of Environmental Enrichment and Methylphenidate Alone and in Combination after Controlled Cortical Impact Injury.
abstract: Environmental enrichment (EE) and methylphenidate (MPH) independently confer significant benefit to behavioral recovery after controlled cortical impact (CCI) injury. Given that combinational therapies may be more clinically translatable than monotherapies, the aim of the current study was to test the hypothesis that a combined treatment regimen of EE and MPH would provide greater therapeutic efficacy than either one alone. Anesthetized adult male rats received either a CCI of moderate severity or sham injury and were then randomly assigned to EE or standard (STD) housing where they received either intraperitoneal (ip) MPH (5 mg/kg) or vehicle (VEH; 1.0 mL/kg; ip) beginning 24 h after injury and once daily for 19 days. Motor and cognitive assessments were conducted on post-injury days 1-5 and 14-19, respectively. No differences were observed in sham controls regardless of treatments, and thus their data were pooled. The traumatic brain injury (TBI)+EE+VEH and TBI+EE+MPH groups exhibited enhanced beam balance and beam walk performance relative to the TBI+STD+VEH group (p < 0.05), but did not differ from one another (p > 0.05). No effect of MPH treatment alone was observed in either motor task. In contrast, MPH improved spatial learning and memory when presented alone and also when combined with EE relative to VEH-treated STD controls (p < 0.05). In addition, both EE groups performed significantly better than the TBI+STD+MPH group (p < 0.05), but did not differ from one another (p > 0.05). These data replicate previous findings that both EE and MPH confer cognitive benefits after TBI and extend the findings by revealing that combining EE and MPH does not produce effects greater than either treatment alone, which does not support the hypothesis. The lack of an additive effect may be because of the robustness of the EE.
authors.affiliation: 1 Physical Medicine and Rehabilitation, University of Pittsburgh , Pittsburgh, Pennsylvania.|2 Safar Center for Resuscitation Research, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Jacob B
authors.initials: JB
authors.lastname: Leary
authors.affiliation: 1 Physical Medicine and Rehabilitation, University of Pittsburgh , Pittsburgh, Pennsylvania.|2 Safar Center for Resuscitation Research, University of Pittsburgh , Pittsburgh, Pennsylvania.|3 Neurobiology, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Corina O
authors.initials: CO
authors.lastname: Bondi
authors.affiliation: 1 Physical Medicine and Rehabilitation, University of Pittsburgh , Pittsburgh, Pennsylvania.|2 Safar Center for Resuscitation Research, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Megan J
authors.initials: MJ
authors.lastname: LaPorte
authors.affiliation: 1 Physical Medicine and Rehabilitation, University of Pittsburgh , Pittsburgh, Pennsylvania.|2 Safar Center for Resuscitation Research, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: Carlson
authors.affiliation: 1 Physical Medicine and Rehabilitation, University of Pittsburgh , Pittsburgh, Pennsylvania.|2 Safar Center for Resuscitation Research, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Hannah L
authors.initials: HL
authors.lastname: Radabaugh
authors.affiliation: 1 Physical Medicine and Rehabilitation, University of Pittsburgh , Pittsburgh, Pennsylvania.|2 Safar Center for Resuscitation Research, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Cheng
authors.affiliation: 1 Physical Medicine and Rehabilitation, University of Pittsburgh , Pittsburgh, Pennsylvania.|2 Safar Center for Resuscitation Research, University of Pittsburgh , Pittsburgh, Pennsylvania.|4 Critical Care Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.|5 Psychology, University of Pittsburgh , Pittsburgh, Pennsylvania.|6 Center for Neuroscience, University of Pittsburgh , Pittsburgh, Pennsylvania.|7 Center for the Neural Basis of Cognition, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Kline
mesh_terms: D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000503:physiopathology / Q000523:psychology / Q000628:therapy*; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D003131:Combined Modality Therapy / Q000379:methods; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D004777:Environment; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D065853:Spatial Learning / Q000187:drug effects / Q000502:physiology*; D016896:Treatment Outcome; D014949:Wounds, Nonpenetrating / Q000503:physiopathology / Q000523:psychology / Q000628:therapy
chemical_list: D018765:Dopamine Uptake Inhibitors; D008774:Methylphenidate
keywords: Morris water maze; behavioral outcome; controlled cortical impact; dopamine agonist; environmental enrichment; functional recovery; learning and memory; traumatic brain injury