Aripiprazole and environmental enrichment independently improve functional outcome after cortical impact injury in adult male rats, but their combination does not yield additional benefits

Abstract Typical antipsychotic drugs (APDs) with D 2 antagonistic properties impede functional outcome after experimental traumatic brain injury (TBI) and reduce the effectiveness of environmental enrichment (EE). Here we test the hypothesis that aripiprazole (ARIP), an atypical APD with partial D 2 and 5-HT 1A receptor agonist activities will improve recovery after TBI and when combined with EE will further enhance the benefits. Anesthetized adult male rats received either a controlled cortical impact of moderate severity or sham injury and then were randomly assigned to EE or standard (STD) housing and once daily intraperitoneal injections of ARIP (0.1 mg/kg) or vehicle (VEH; 1.0 mL/kg) beginning 24 h after injury for 19 days. Motor (beam-walking time and beam-walk score) and cognitive (acquisition of spatial learning and memory) outcomes were assessed on post-operative 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 housing or treatment, so the data were pooled. The SHAM group performed better than all TBI groups on motor and spatial learning ( p p p  > 0.05). The ARIP-treated STD group performed better than the VEH-treated STD group on beam-walk score and spatial learning ( p p  > 0.05). Cortical lesion volume was smaller in all treated groups compared to the TBI + STD + VEH group ( p 2 receptor antagonism, ARIP does not impede rehabilitation (i.e., EE).