Amantadine ameliorates dopamine-releasing deficits and behavioral deficits in rats after fluid percussion injury.
OBJECTIVE
To investigate the role of dopamine in cognitive and motor learning skill deficits after a traumatic brain injury (TBI), we investigated dopamine release and behavioral changes at a series of time points after fluid percussion injury, and explored the potential of amantadine hydrochloride as a chronic treatment to provide behavioral recovery.


METHODS
In this study, we sequentially investigated dopamine release at the striatum and behavioral changes at 1, 2, 4, 6, and 8 weeks after fluid percussion injury. Rats subjected to 6-Pa cerebral cortical fluid percussion injury were treated by using subcutaneous infusion pumps filled with either saline (sham group) or amantadine hydrochloride, with a releasing rate of 3.6 mg/kg/hour for 8 weeks. The dopamine-releasing conditions and metabolism were analyzed sequentially by fast scan cyclic voltammetry (FSCV) and high-pressure liquid chromatography (HPLC). Novel object recognition (NOR) and fixed-speed rotarod (FSRR) behavioral tests were used to determine treatment effects on cognitive and motor deficits after injury.


RESULTS
Sequential dopamine-release deficits were revealed in 6-Pa-fluid-percussion cerebral cortical injured animals. The reuptake rate (tau value) of dopamine in injured animals was prolonged, but the tau value became close to the value for the control group after amantadine therapy. Cognitive and motor learning impairments were shown evidenced by the NOR and FSRR behavioral tests after injury. Chronic amantadine therapy reversed dopamine-release deficits, and behavioral impairment after fluid percussion injuries were ameliorated in the rats treated by using amantadine-pumping infusion.


CONCLUSIONS
Chronic treatment with amantadine hydrochloride can ameliorate dopamine-release deficits as well as cognitive and motor deficits caused by cerebral fluid-percussion injury.
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan.
Eagle Yi-Kung
EY
Huang
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan.
Pi-Fen
PF
Tsui
Graduate Institute of Computer and Communication Engineering, National Taipei University of Technology, Taipei, Taiwan.
Tung-Tai
TT
Kuo
Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Jing-Jr
JJ
Tsai
School of Public Health, National Defense Medical Center, Taipei, Taiwan.
Yu-Ching
YC
Chou
Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Hsin-I
HI
Ma
Department of Neurosurgery, Taipei Medical University Hospital, the PhD Program for Neural Regenerative Medicine, Graduate Institute of Neural Regenerative Medicine, Taipei Medical University, Taipei, Taiwan.
Yung-Hsiao
YH
Chiang
Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Yuan-Hao
YH
Chen
D000547:Amantadine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D003071:Cognition / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D008297:Male; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects; D045442:Rotarod Performance Test; D009435:Synaptic Transmission
D015259:Dopamine Agents; D000547:Amantadine; D004298:Dopamine