COGNITIVE IMPAIRMENT FOLLOWING TRAUMATIC BRAIN INJURY - THE EFFECT OFPRE-INJURY AND POSTINJURY ADMINISTRATION OF SCOPOLAMINE AND MK-801

In order to examine the effectiveness of pre- and post-injury administ ration of muscarinic cholinergic and NMDA antagonists in reducing cogn itive deficits following traumatic brain injury (TBI), rats were injec ted with either scopolamine (1 mg/kg) or MK-801 (0.3 mg/kg) 15 min pri or to or 15 min after fluid percussion TBI. Cognitive performance was assessed with the Morris water maze procedure on days 11-15 after TBI or sham injury. When scopolamine and MK-801 were injected 15 min befor e injury, Morris water maze deficits were significantly reduced (P < 0 .01 and P < 0.05, respectively). When scopolamine and MK-801 were inje cted 15 min after TBI, neither drug was effective in attenuating Morri s water maze deficits. Consistent with other research, these results s uggest that the cognitive deficits produced by TBI are the consequence of a brief period of excessive excitation of cholinergic and NMDA rec eptor systems. The results of this experiment also suggest that the te mporal therapeutic window for the treatment of cognitive dysfunction w ith receptor antagonist intervention appears to be quite brief (< 15 m in) in the rat.