Ho Ming-Che, Cherng Chianfang G, Tsai Yen-Ping N, Chiang Chih-Yuan, Chuang Jia-Ying, Kao Shu-Fang, Yu Lung
Institute of Behavioral Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan, 70101, Republic of China.
Psychopharmacology (Berl). 2009 Jul;205(1):141-9. doi: 10.1007/s00213-009-1524-5. Epub 2009 Apr 3.
Whether monoamine oxidase inhibitors (MAOIs) can be used to suppress the reinforcing effect of cocaine remains unknown. This study was undertaken to examine effects of a long-term dosing regimen with selective MAOIs on cocaine and food reward.
Since single dose of clorgyline (2 mg/kg), deprenyl (1 mg/kg), and pargyline (10 mg/kg) did not acutely affect mouse locomotor activity, these doses were chosen to treat the male C57BL/6j mice on a daily basis.
Fourteen consecutive days of pretreatments with clorgyline, deprenyl, or pargyline (one injection per day) did not affect natural reward-supported operant behavior, since acquisition of the lever pressing responses for food pellets under an FR-1 protocol did not differ among these drug- and saline-treated mice. Likewise, 24 consecutive days of pretreatments with clorgyline did not alter acquisition of the cocaine (0.3 mg/kg per infusion)-supported operant responses under an FR-1 protocol. In contrast, 24 days of pretreatments with deprenyl and pargyline abolished the cocaine-supported operant responses under a similar protocol. Twenty-four days of clorgyline treatment enhanced serotonin contents in striatum, nucleus accumbens, and frontal cortex. Frontal cortical 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacidic acid concentrations were decreased following 24 days of pretreatments with deprenyl and pargyline. These changes were not evident in mice pretreated with clorgyline.
We suggest that long-term treatments with MAO-B inhibitors may decrease cocaine-supported operant responses in cocaine-naïve mice by selectively decreasing frontal cortical metabolism of dopamine and serotonin.
单胺氧化酶抑制剂（MAOIs）是否可用于抑制可卡因的强化作用尚不清楚。本研究旨在探讨长期给予选择性MAOIs对可卡因和食物奖赏的影响。
由于单剂量的氯吉兰（2mg/kg）、司来吉兰（1mg/kg）和帕吉林（10mg/kg）对小鼠自发活动无急性影响，故选择这些剂量每日对雄性C57BL/6j小鼠进行处理。
连续14天用氯吉兰、司来吉兰或帕吉林预处理（每日注射一次）不影响自然奖赏支持的操作性行为，因为在固定比率为1（FR-1）的实验方案下，这些药物处理组和生理盐水处理组小鼠获取食物颗粒的杠杆按压反应并无差异。同样，连续24天用氯吉兰预处理也未改变在FR-1实验方案下可卡因（每次输注0.3mg/kg）支持的操作性反应的获取。相比之下，在类似实验方案下，连续24天用司来吉兰和帕吉林预处理消除了可卡因支持的操作性反应。氯吉兰处理24天可提高纹状体、伏隔核和额叶皮质中的5-羟色胺含量。司来吉兰和帕吉林预处理24天后，额叶皮质3,4-二羟基苯乙酸和5-羟吲哚乙酸浓度降低。这些变化在氯吉兰预处理的小鼠中不明显。
我们认为，长期用MAO-B抑制剂治疗可能通过选择性降低多巴胺和5-羟色胺在额叶皮质的代谢，减少未接触过可卡因的小鼠中可卡因支持的操作性反应。
