MUSCARINIC CHOLINERGIC RECEPTOR-BINDING IN RAT-BRAIN AT 15 DAYS FOLLOWING TRAUMATIC BRAIN INJURY

Laboratory studies indicate that activation of muscarinic cholinergic receptors (mAChRs) at or soon after traumatic brain injury (TBI) signi ficantly contributes to behavioral morbidity. Recent research has demo nstrated that pre-injury treatment with the muscarinic antagonist scop olamine significantly reduces spatial memory deficits at 11-15 days po st-TBI. In the present study, we examined mAChR binding kinetics in br ain regions at 15 days after moderate (1.95 atm) fluid percussion TBI in untreated and scopolamine-treated rats. Three groups were examined: untreated TBI (n = 8), TBI with pre-injury scopolamine treatment (1.0 mg/kg, i.p., 15 min prior to injury) (n = 11), and sham-injury (n = 7 ). The affinity (K-d) and maximum number of binding sites (B-max) of m AChRs in hippocampus, neocortex, and brainstem were determined by [H-3 ]QNB binding. B-max values in TBI animals were significantly higher in hippocampus (4061 +/- 494 fmol/mg protein) and neocortex (4272 +/- 64 0 fmol/mg protein), but not in brainstem (833 +/- 39 fmol/mg protein) compared to sham-injured controls (hipp. 2812 +/- 218 fmol/mg/protein; neoctx. 2850 +/- 129 fmol/mg protein; brainstem 794 +/- 26 fmol/mg pr otein) (P < 0.05). At 15 days after injury, B-max values of mAChRs in TBI animals with pre-injury scopolamine treatment (hipp. 2850 +/- 129 fmol/mg protein; neoctx. 2948 +/- 123 fmol/mg protein) did not differ from control. In all brain regions, K-d values did not differ between groups. These results demonstrate that TBI significantly alters the bi nding sites of mAChRs in hippocampus and neocortex for as long as 15 d ays after TBI. Furthermore, these results indicate that a pharmacologi cal treatment that improves motor and memory function outcome also nor malizes aspects of mAChRs physiology. These data suggest that excessiv e activation of mAChRs at or soon after TBI impact contributes to long -term pathophysiological processes in TBI.