REDUCED EVOKED RELEASE OF ACETYLCHOLINE IN THE RODENT HIPPOCAMPUS FOLLOWING TRAUMATIC BRAIN INJURY

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 lat eral controlled cortical impact (n = 10) or sham surgery (n = 10). Pri or to microdialysis, behavioral assessments of motor and spatial memor y were performed. Cortical impact (6 meter/s, 2 mm deformation) produc ed beam balance deficits that persisted for 1 day and beam walking def icits that persisted for 3 days after injury. In addition, spatial mem ory, as measured by swim latencies in a Morris water maze, was comprom ised between 10-14 days after injury. Immediately following behavioral testing, the animals were anesthetized with halothane, and a microdia lysis probe was placed into the dorsal hippocampus. After a 160 min eq uilibration period, extracellular levels of acetylcholine were measure d prior to and after an intraperitoneal administration of scopolamine (1 mg/kg), which evokes acetylcholine release by blocking autoreceptor s. Prior to scopolamine administration, there were no differences in e xtracellular levels of acetylcholine between injured and sham animals. However, there was a significant reduction of hippocampal acetylcholi ne release evoked by scopolamine in injured animals as compared to sha m controls. In separate control groups, saline administration alone di d not change hippocampal acetylcholine release in injured(n = 5) or sh am (n = 5) animals. This study represents the first application of in vivo microdialysis to evaluate chronic neurotransmission deficits foll owing TBI. The present study demonstrates that a magnitude of traumati c 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 mech anisms mediating release of acetylcholine could play a significant rol e in cholinergic neurotransmission deficits following TBI.