title: Reduced evoked release of acetylcholine in the rodent hippocampus following traumatic brain injury.
abstract: The chronic effects of traumatic brain injury on acetylcholine release were evaluated by using in vivo microdialysis. Acetylcholine release was measured in the hippocampus of anesthetized rats 2 weeks after lateral controlled cortical impact (n = 10) or sham surgery (n = 10). Prior to microdialysis, behavioral assessments of motor and spatial memory were performed. Cortical impact (6 meter/s, 2 mm deformation) produced beam balance deficits that persisted for 1 day and beam walking deficits that persisted for 3 days after injury. In addition, spatial memory, as measured by swim latencies in a Morris water maze, was compromised between 10-14 days after injury. Immediately following behavioral testing, the animals were anesthetized with halothane, and a microdialysis probe was placed into the dorsal hippocampus. After a 160 min equilibration period, extracellular levels of acetylcholine were measured prior to and after an intraperitoneal administration of scopolamine (1 mg/kg), which evokes acetylcholine release by blocking autoreceptors. Prior to scopolamine administration, there were no differences in extracellular levels of acetylcholine between injured and sham animals. However, there was a significant reduction of hippocampal acetylcholine release evoked by scopolamine in injured animals as compared to sham controls. In separate control groups, saline administration alone did not change hippocampal acetylcholine release in injured (n = 5) or sham (n = 5) animals. This study represents the first application of in vivo microdialysis to evaluate chronic neurotransmission deficits following TBI. The present study demonstrates that a magnitude of traumatic brain injury (TBI) sufficient to produce spatial memory deficits can result in a reduction in scopolamine-evoked release of acetylcholine within the hippocampus. The data further suggest that presynaptic mechanisms mediating release of acetylcholine could play a significant role in cholinergic neurotransmission deficits following TBI.
authors.affiliation: Department of Neurosurgery, University of Texas Health Science Center at Houston 77030, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Dixon
authors.forename: J
authors.initials: J
authors.lastname: Bao
authors.forename: D A
authors.initials: DA
authors.lastname: Long
authors.forename: R L
authors.initials: RL
authors.lastname: Hayes
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001930:Brain Injuries / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D018782:Maze Learning / Q000187:drug effects; D017551:Microdialysis; D051381:Rats; D012601:Scopolamine / Q000494:pharmacology; D013997:Time Factors
chemical_list: D012601:Scopolamine; D000109:Acetylcholine