The neurobehavioral benefit conferred by a single systemic administration of 8-OH-DPAT after brain trauma is confined to a narrow therapeutic window.
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.
Cheng
Jeffrey P
JP
Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Aslam
Haris A
HA
Hoffman
Ann N
AN
Zafonte
Ross D
RD
Kline
Anthony E
AE
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001930:Brain Injuries / Q000188:drug therapy*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage*; D013997:Time Factors
D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin