The neurobehavioral benefit conferred by a single systemic administration of 8-OH-DPAT after brain trauma is confined to a narrow therapeutic window

Abstract

The 5-HT(1A) receptor agonist 8-OH-DPAT (0.5mg/kg) enhances behavioral recovery when administered 15min after experimental traumatic brain injury (TBI). To determine if benefits are still attainable at clinically relevant times, treatment was delayed 1 and 2h post-TBI and motor/cognitive performance was compared to early (i.e., 15min) administration. No differences were observed among the vehicle and 8-OH-DPAT groups treated at 1 and 2h, but all three were significantly impaired versus early 8-OH-DPAT. The data suggest that an early and narrow critical period exists for the behavioral recovery afforded by a single 8-OH-DPAT treatment paradigm. The critical window corresponds to the well documented TBI-induced glutamate increase, suggesting that 8-OH-DPAT may be conferring neuroprotection by attenuating this acute deleterious surge.

Fig. 1

Mean (± SE) vestibulomotor ability as measured by time (sec) to balance on an elevated wooden beam prior to, and after, TBI or SHAM injury. *P < 0.05 vs. TBI + VEHICLE. **P < 0.05 vs. TBI + VEHICLE, TBI + 8-OH-DPAT (1 hr), and TBI + 8-OH-DPAT (2 hr).

Fig. 2

Mean (± SE) time (sec) to locate escape platform in the Morris water maze on post-TBI days 14-18. *P < 0.05 vs. TBI + VEHICLE, TBI + 8-OH-DPAT (1 hr), and TBI + 8-OH-DPAT (2 hr). **P < 0.05 vs. all TBI groups.