Amantadine ameliorates dopamine-releasing deficits and behavioral deficits in rats after fluid percussion injury

• Published in: PloS one 2014-01, Vol.9 (1), p.e86354-e86354
• Main Authors: Huang, Eagle Yi-Kung, Tsui, Pi-Fen, Kuo, Tung-Tai, Tsai, Jing-Jr, Chou, Yu-Ching, Ma, Hsin-I, Chiang, Yung-Hsiao, Chen, Yuan-Hao
• Format: Article
• Language: English
• Subjects: Amantadine; Amantadine - pharmacology; Amantadine - therapeutic use; Animals; Biology; Brain; Brain injuries; Brain Injuries - drug therapy; Brain Injuries - metabolism; Brain Injuries - psychology; Chromatography; Cognition - drug effects; Cognitive ability; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Cortex; Dopamine; Dopamine - physiology; Dopamine Agents - pharmacology; Dopamine Agents - therapeutic use; Drug Evaluation, Preclinical; Head injuries; High performance liquid chromatography; Infusion; Kinases; Liquid chromatography; Male; Materials recovery; Medicine; Metabolism; Motor skill; Motor skill learning; Neostriatum; Object recognition; Pattern recognition; Percussion; Phenols (Class of compounds); Product introduction; Rats; Rats, Sprague-Dawley; Recognition (Psychology) - drug effects; Releasing; Rodents; Rotarod Performance Test; Social and Behavioral Sciences; Synaptic Transmission; Therapy; Traumatic brain injury
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0086354

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. 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. 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. Chronic treatment with amantadine hydrochloride can ameliorate dopamine-release deficits as well as cognitive and motor deficits caused by cerebral fluid-percussion injury.