Affiliations: Department of Neurosurgery, University of Pittsburgh
Medical Center, PA, USA | Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh. Pittsburgh, PA, USA
Note: [] Correspondence: Brain Trauma Research Center, Department of
Neurosurgery, University of Pittsburgh, 3434 Fifth Ave., Suite 201, Pittsburgh,
PA 15260, USA. Phone: +1-412-383-2188; Fax: +1-412-624-0943; E-mail:
edixon@neuronet.pitt.edu
Abstract: Amantadine, a dopamine agonist, is reported to have beneficial
effects on the neurobehavioral sequelae of clinical brain injury. However,
there are currently no published laboratory reports on its use in the
assessment of functional or histopathological outcome following experimental
traumatic brain injury (TBI). To this end, we examined the effects of daily
amantadine treatment on functional recovery (motor and Morris water maze
performance) and hippocampal neuronal survival following controlled cortical
impact (CCI) injury (4 meters/sec, 2.7 mm tissue deformation). Male
Sprague-Dawley rats were pretrained on motor performance tasks (beam balance
and beam walking) one day prior to injury and tested on post-operative days
15. Additionally, all subjects were trained on the Morris water maze on
post-operative days 1418. Beginning one day after CCI injury or sham
surgery, animals were injected once daily for 18 days with either amantadine
(10 mg/kg, i.p.) or saline. The amantadine treatment regimen was ineffective in
promoting motor recovery and increasing survival of hippocampal neurons in both
the CA1 and CA3 regions following TBI, but did show improved swim latencies
during the five days of water maze testing (Day 14 vs. Day 18, p < 0.01)
when compared to saline controls. Mean (± SE) swim latencies on Day 18
were 15.12 ± 2.8, 13.25 ± 4.18, 70.83 ± 11.1, and 38.5
± 3.55 sec for the sham/saline, sham/amantadine, injured/saline, and
injured/amantadine treatment groups, respectively. Thus, while the daily
administration of amantadine exhibited a neutral effect on motor behavior, it
produced a modest attenuation of water maze performance deficits. This latter
finding is consistent with published clinical data suggesting a beneficial
effect on functional outcome with amantadine therapy.
Keywords: brain injury, amantadine, dopamine , rat
