A delayed and chronic treatment regimen with the 5-HT1A receptor agonist 8-OH-DPAT after cortical impact injury facilitates motor recovery and acquisition of spatial learning.

An early (i.e., 15min) single systemic administration of the 5-HT(1A) receptor agonist 8-OH-DPAT enhances behavioral recovery after experimental traumatic brain injury (TBI). However, acute administration of pharmacotherapies after TBI may be clinically challenging and thus the present study sought to investigate the potential efficacy of a delayed and chronic 8-OH-DPAT treatment regimen. Forty-eight isoflurane-anesthetized adult male rats received either a controlled cortical impact or sham injury and beginning 24h later were administered 8-OH-DPAT (0.1 or 0.5mg/kg) or saline vehicle (1.0mL/kg) intraperitoneally once daily until all behavioral assessments were completed. Neurobehavior was assessed by motor and cognitive tests on post-operative days 1-5 and 14-19, respectively. The lower dose of 8-OH-DPAT (0.1mg/kg) enhanced motor performance, acquisition of spatial learning, and memory retention vs. both the higher dose (0.5mg/kg) and vehicle treatment (p<0.05). These data replicate previous findings from our laboratory showing that 8-OH-DPAT improves neurobehavior after TBI, and extend those results by demonstrating that the benefits can be achieved even when treatment is withheld for 24h. A delayed and chronic treatment regimen may be more clinically feasible.