EFFECT OF PRIOR RECEPTOR ANTAGONISM ON BEHAVIORAL MORBIDITY PRODUCED BY COMBINED FLUID PERCUSSION INJURY AND ENTORHINAL CORTICAL LESION

We have used an animal model of traumatic brain injury (TBI) that inco rporates both the neurotransmitter toxicity of fluid percussion TBI an d deafferentation of bilateral entorhinal cortical (BEC) lesion to exp lore whether administration of muscarinic cholinergic or N-methyl-D-as partate glutamatergic antagonists prior to injury ameliorates cognitiv e morbidity. Fifteen minutes prior to moderate central fluid percussio n TBI, rats were given intraperitoneal injections of either scopolamin e (1.0 mg/kg) or MK-801 (0.3 mg/kg) and 24 hr later underwent BEC lesi on. Body weight was followed for 5 days postinjury, as was beam balanc e and beam walk performance to assure motor recovery prior to spatial memory testing. Each group was assessed for spatial memory deficits wi th the Morris water maze at short term (days 11-15) and long-term (60- 64 days) postinjury intervals and then compared with untreated combine d insult and sham-injured controls. Results showed that each drug sign ificantly elevated body weight relative to untreated injured cases. Bo th scopolamine and MK-gOl reduced beam balance deficits, whereas neith er drug had a significant effect on beam walk deficits. Interestingly, short-term cognitive deficits assessed on days 11-15 were differentia lly affected by the two drugs: MK-801 pretreatment enhanced the recove ry of spatial memory performance, whereas scopolamine pretreatment did not. Long-term (days 60-64) deficits in spatial memory were not alter ed by pretreatment with either drug. Our results suggest that, unlike fluid percussion TBI alone, behavioral impairment may require more sel ect intervention when deafferentation is part of the head trauma patho logy. (C) 1997 Wiley-Liss, Inc.