Betaine and sodium benzoate modulate the reinforcement and relapse of ketamine self-administration

• Main Authors: LEE, MEI-YI, 李美儀
• Other Authors: CHEN, HWEI-HSIEN
• Format: Others
• Language: zh-TW
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/eugng4

博士 === 慈濟大學 === 藥理暨毒理學碩士班/博士班 === 106 === Background: Abuse of ketamine is a severe health problem in Taiwan. It’s an important issue to find potential treatment for ketamine addiction. The reinforcing effects of ketamine is thought to involve NMDA (N-methyl-D-aspartate) receptor blockade. The current study determined whether betaine, a derivative of glycine, and sodium benzoate, a D-amino acid oxidase (DAAO) inhibitor, modulate NMDA receptor function and reduce the reinforcement and relapse of ketamine. Methods: The extracellular recording of MED 64 system ( med 64 multi-electrode array system) in the mouse prefrontal cortical slices was used to assess if betaine and sodium benzoate could replace glycine to evoked NMDA receptors mediated excitatory filed potentials. In addition, intravenous self-administration of ketamine in rats was used to estimate the effects of betaine and sodium benzoate treatment on ketamine self-administration, extinction and reinstatement. Results: Our studies showed that betaine and sodium benzoate combined with glutamate could evoke NMDA receptor-mediated excitatory filed potentials. However, similar to the DAAO inhibitor compound 8, the onset of sodium benzoate to increase excitatory filed potential was delayed, suggesting that the enhancement of NMDA receptors-mediated excitatory filed potential through increasing D-serine levels. In ketamine self-administration rats, betaine and sodium benzoate diminished the reinforcing efficacy of ketamine in FR (fix ratio) and PR (profrassive ratio) schedules in a dose dependent manner. Treatment of betaine and sodium benzoate during extinction training or forced abstinence in the home cage for 5 days significantly reduced the reinstatement of ketamine seeking behavior. However, these two compounds did not affect the reinforcement and relapse of food. Conclusion:These findings suggest that betaine and sodium benzoate might have potential for treatment of ketamine addiction.