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 incorporates both the neurotransmitter toxicity of fluid percussion TBI and deafferentation of bilateral entorhinal cortical (BEC) lesion to explore whether administration of muscarinic cholinergic or N‐methyl‐D‐aspartate glutamatergic antagonists prior to injury ameliorates cognitive morbidity. Fifteen minutes prior to moderate central fluid percussion TBI, rats were given intraperitoneal injections of either scopolamine (1.0 mg/kg) or MK‐801 (0.3 mg/kg) and 24 hr later underwent BEC lesion. Body weight was followed for 5 days postinjury, as was beam balance and beam walk performance to assure motor recovery prior to spatial memory testing. Each group was assessed for spatial memory deficits with the Morris water maze at short term (days 11–15) and long‐term (60–64 days) postinjury intervals and then compared with untreated combined insult and sham‐injured controls. Results showed that each drug significantly elevated body weight relative to untreated injured cases. Both scopolamine and MK‐801 reduced beam balance deficits, whereas neither drug had a significant effect on beam walk deficits. Interestingly, short‐term cognitive deficits assessed on days 11–15 were differentially affected by the two drugs: MK‐801 pretreatment enhanced the recovery of spatial memory performance, whereas scopolamine pretreatment did not. Long‐term (days 60–64) deficits in spatial memory were not altered by pretreatment with either drug. Our results suggest that, unlike fluid percussion TBI alone, behavioral impairment may require more select intervention when deafferentation is part of the head trauma pathology. J. Neurosci. Res. 49:197–206, 1997. © 1997 Wiley‐Liss, Inc.