Amantadine improves water maze performance without affecting motor behavior following traumatic brain injury in rats

Amantadine, a dopamine agonist, is reported to have beneficial effects on t he neurobehavioral sequelae of clinical brain injury. However, there are cu rrently no published laboratory reports on its use in the assessment of fun ctional or histopathological outcome following experimental traumatic brain injury (TBI). To this end, we examined the effects of daily amantadine tre atment on functional recovery (motor and Morris water maze performance) and hippocampal neuronal survival following controlled cortical impact (CCI) i njury (4 meters/sec, 2.7 mm tissue deformation). Male Sprague-Dawley rats w ere pretrained on motor performance tasks (beam balance and beam walking) o ne 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 inj ected once daily for 18 days with either amantadine (10 mg/kg, i.p.) or sal ine. The amantadine treatment regimen was ineffective in promoting motor re covery and increasing survival of hippocampal neurons in both the CA1 and C A3 regions following TBI, but did show improved swim latencies during the f ive 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/sal ine, sham/amantadine, injured/saline, and injured/amantadine treatment grou ps, respectively. Thus, while the daily administration of amantadine exhibi ted a neutral effect on motor behavior, it produced a modest attenuation of water maze performance deficits. This latter finding is consistent with pu blished clinical data suggesting a beneficial effect on functional outcome with amantadine therapy.