Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
Board

It is well-documented that a single dose of drugs that reduce noradrenergic transmission can reinstate hemiplegia 30 days after recovery from brain injury in the rat [4,6,7,12]and up to 8 months after injury in the cat [5]. This is illustrated in a movie posted on the Internet at the following web site:

http://www.unm.edu/~feeney/index.html

However, no systematic studies have determined the length of time after recovery in which injured animals are vulnerable to such reinstatement effects. Further, no study has determined whether tolerance to such drugs occurs with multiple injections. The current study used a within-subject design in two experiments to address these questions. The first experiment used a within-subject dose-response to determine whether the vulnerability to reinstatement by prazosin, an alpha-1 noradrenergic antagonist, diminishes over time (1, 3, 6, & 12 months) after injury. Propranolol and saline groups controlled for receptor, sedation, and injection volume effects on three tasks: beam walk, vibrissae-evoked, and forelimb-evoked tactile placing. A cross-over study where all animals were given prazosin was conducted after the 12 month data point. The second experiment, using different animals, sought to determine whether there was a tolerance to the reinstatement effect, measured by a beam walk task, by administering 3 injections spaced 3 hours apart of either prazosin or clonidine, an alpha-2 noradrenergic agonist 30 days after injury, then crossing over drug groups 1 week later.

We hypothesized that prazosin, but not propranolol, administered to recovered rats would reinstate hemiplegia in a dose-dependent manner at 1, 3, 6 & 12 months post-injury. We also hypothesized that recovered rats would have a diminishing response to closely spaced multiple injections of both clonidine and prazosin.

Back to the top.