title: Amantadine improves water maze performance without affecting motor behavior following traumatic brain injury in rats.
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 1-5. Additionally, all subjects were trained on the Morris water maze on post-operative days 14-18. 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.
authors.affiliation: Department of Neurosurgery, University of Pittsburgh Medical Center, PA, USA.
authors.forename: C. Edward
authors.initials: CE
authors.lastname: Dixon
authors.forename: Marilyn F.
authors.initials: MF
authors.lastname: Kraus
authors.forename: Anthony E.
authors.initials: AE
authors.lastname: Kline
authors.forename: Xiecheng
authors.initials: X
authors.lastname: Ma
authors.forename: Hong Q.
authors.initials: HQ
authors.lastname: Yan
authors.forename: Raymond G.
authors.initials: RG
authors.lastname: Griffith
authors.forename: Brian M.
authors.initials: BM
authors.lastname: Wolfson
authors.forename: Donald W.
authors.initials: DW
authors.lastname: Marion