TRAUMATIC BRAIN INJURY CAUSES A DECREASE IN M2 MUSCARINIC CHOLINERGICRECEPTOR-BINDING IN THE RAT-BRAIN

Numerous studies indicate that an acute, excessive activation of musca rinic acetylcholine receptors (mAChR) contributes to the pathophysiolo gical sequela of TBI. The present study examined the effect of moderat e fluid percussion traumatic brain injury (TBI) on binding to M1 and M 2 mAChR subtypes in the hippocampal formation and adjacent cortex usin g quantitative autoradiography. Injured animals along with concurrent controls were sacrificed by in situ freezing at 3 h or 24 h following TBI. Slide-mounted tissue sections were incubated in either [H-3]piren zipine (23 nM) for M1 or [H-3]AFDX384 (9 nM) for M2 mAChR subtype labe ling. Binding of [H-3]pirenzipine to the M1 mAChR subtype was not sign ificantly altered by TBI when compared to sham-injured animals. [H-3]A FDX384 binding to the M2 mAChR subtype was significantly decreased at 24 h in hippocampal CA2-3 region and dorsal blade of the dentate gyrus (P < 0.05). The differences observed between M1 and M2 subtypes sugge sts that these muscarinic subtypes may differentially contribute to th e pathophysiology of TBI.