Traumatic brain injury (TBI) initiates immediate and secondary neuropathological cascades that can result in persistent neurological dysfunction. Previous studies from our laboratory have shown that experimental rat brain injury causes a rapid and persistent decrease in CNS α7* nicotinic cholinergic receptor (nAChr) expression. The purpose of this study was to investigate whether intermittent nicotine injections could improve cognitive performance in the Morris water maze (MWM) following experimental brain injury. Adult male rats were anesthetized and subjected to a 1.5 mm controlled cortical impact (CCI) injury of the somatosensory cortex. Animals received twice daily i.p. nicotine injections for 11 days prior to CCI, 11 days following CCI or during both pre- and post-surgical intervals. MWM training was initiated 12 days post-injury. In the training phase of cognitive testing, twice-daily nicotine treatment following injury attenuated trauma-induced deficits in the distance traveled to reach the escape platform. This group of animals also had improvements in several measures of the probe test, including time spent, distance traveled and total entries into the target quadrant. TBI caused significant deficits in α7* nAChr expression in several regions of the hippocampus and cerebral cortex, which were largely unaffected by intermittent nicotine treatment. However, nicotine treatment up-regulated [3H]-epibatidine binding to non-α7* nAChrs, attenuating TBI-induced deficits in receptor expression in several brain regions evaluated. These results suggest that nicotine is efficacious at attenuating CCI-induced cognitive deficits in a manner independent of changes in α7* nAChr expression, perhaps via up-regulation of non-α7* nAChrs.
|Number of pages||10|
|State||Published - Jul 16 2003|
Bibliographical noteFunding Information:
This research was supported by a grant from the Kentucky Spinal Cord and Head Injury Research Trust (J.R.P.) and the National Institutes of Health (NS39828 to S.W.S. and NS42196 to J.R.P.). The authors thank Mr. James Hobbs Jr. for technical assistance with these experiments.
- Morris water maze
- α7* nicotinic receptor
ASJC Scopus subject areas
- Neuroscience (all)