Environmental enrichment (EE) and
serotonin(1A) (5-HT(1A))-receptor agonists provide significant benefit after experimental
traumatic brain injury (TBI). The aim of this study was to test the hypothesis that combining these
therapies would produce an effect that is more robust than either
therapy alone. Anesthetized adult male rats received a cortical impact or
sham injury and then were randomly assigned to EE or standard (STD) housing where they received either
buspirone (0.3 mg/kg) or vehicle (1.0 mL/kg) once daily for 3 weeks. Motor and cognitive assessments were conducted on post-injury days 1-5 and 14-19, respectively. CA1/3 neurons were quantified at 3 weeks. No differences were observed among
buspirone and vehicle
sham groups in any task regardless of housing condition and thus the data were pooled. CA3 cell loss was reduced in the TBI+EE+
buspirone and TBI+EE+vehicle groups. Motor recovery, spatial learning, and memory retention were enhanced in the TBI+EE+
buspirone, TBI+EE+vehicle, and TBI+STD+
buspirone groups versus the TBI+STD+vehicle group (p ≤ 0.005). Moreover, spatial learning was significantly better in the TBI+EE+
buspirone group versus the TBI+STD+
buspirone group (p<0.0001). No differences were revealed between the
buspirone and vehicle EE groups. These data show that EE and
buspirone benefit functional outcome after TBI, but their combination is not more robust than either alone, which does not support the hypothesis. The lack of an additive effect may be due to the early-and-continuous EE paradigm on its own producing marked benefits, resulting in a ceiling effect. The evaluation of
buspirone in a delayed-and-abbreviated EE paradigm is ongoing in our laboratory.