AMPHETAMINE AFFECTS THE BEHAVIORAL OUTCOME OF LATERAL FLUID PERCUSSION BRAIN INJURY IN THE RAT

This study examined the effects of (D)-amphetamine, methoxamine (an a1 -adrenergic receptor agonist), and prazosin (an a1-adrenergic receptor antagonist) on the behavioral outcome of lateral fluid percussion bra in injury. Rats trained to perform a beam walking task were subjected to brain injury of moderate severity (2.1-2.2 atm). At 10 min after in jury, rats were treated with amphetamine, methoxamine or prazosin at t wo different dose levels. Amphetamine-treated animals displayed signif icantly lower impairment in beam walking ability from days 1 to 5 afte r brain injury. Neither methoxamine nor prazosin significantly affecte d the impairment in beam walking ability from day 1 to day 7 after inj ury. However, prazosin treatment at both dose levels increased the pos t-injury mortality and the incidences of failure to recovery from hemi plegia. Amphetamine-treatment at 4 mg/kg, but not at 2 mg/kg, improved the spatial learning abilities of the injured animals. Neither methox amine nor prazosin affected the spatial learning abilities. These resu lts indicate that amphetamine facilitated beam walking recovery and im proved cognitive function after concussive fluid percussion injury. Al though the methoxamine experiments suggest that the norepinephrine-alp ha(1)-adrenergic receptor system may not be involved in the pathophysi ology of fluid percussion brain injury, our results with amphetamine ( beneficial effects) and prazosin (deleterious effects) and the results observed in other models of brain injury point out that further inves tigations are necessary to understand the role of a1-adrenergic recept ors in brain injury.