Environmental enrichment and amantadine confer individual but nonadditive enhancements in motor and spatial learning after controlled cortical impact injury.

Environmental enrichment (EE) and amantadine (AMT) enhance motor and cognitive outcome after experimental traumatic brain injury (TBI). However, there are no data on the effects of combining these two therapies. Hence, the aim of the current study was to combine EE and AMT after TBI to determine if their net effect further enhances motor and cognitive performance. Anesthetized adult male rats received either a cortical impact of moderate severity or sham injury and then were randomly assigned to EE or standard (STD) housing and once daily administration of AMT (20 mg/kg; i.p.) or saline vehicle (VEH, 1 mL/kg; i.p.) beginning 24 h after injury for 19 days. Motor and cognitive function were assessed on post-surgical days 1-5 and 14-19, respectively. Cortical lesion volume was quantified on day 21. There were no statistical differences among the sham groups regardless of therapy, so the data were pooled. EE, AMT, and their combination (EE + AMT) improved beam-balance, but only EE and EE + AMT enhanced beam-walking. All three treatment paradigms improved spatial learning and memory relative to the VEH-treated STD controls (p < 0.05). No differences were revealed between the EE groups, regardless of treatment, but both were better than the AMT-treated STD group on beam-walking and spatial learning (p < 0.05). Both EE groups equally reduced cortical lesion volume relative to the STD-housed AMT and VEH groups (p < 0.05). The results indicate that although beneficial on their own, EE + AMT do not provide additional benefits after TBI. It is important to note that the lack of additive effects using the current treatment and behavioral protocols does not detract from the benefits of each individual therapy. The findings provide insight for future combination studies.