The monoamine oxidase (MAO) inhibitor tranylcypromine enhances nicotine self-administration in rats through a mechanism independent of MAO inhibition.
The monoamine oxidase (MAO) inhibitor tranylcypromine enhances nicotine self-administration in rats through a mechanism independent of MAO inhibition.
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DOI：
10.1016/j.neuropharm.2011.03.007
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发表时间：
2011-07
影响因子：
4.7
通讯作者：
Leslie, Frances M.
中科院分区：
文献类型：
--
作者：
Lotfipour, Shahrdad;Arnold, Monica M.;Hogenkamp, Derk J.;Gee, Kelvin W.;Belluzzi, James D.;Leslie, Frances M.
我们目前的研究旨在评估TCP介导的尼古丁自我给药增强的机制。我们重复了之前的研究结果，即与给药鼠相比，TCP预处理1小时（3mg/kg, i.p）可增强尼古丁自我给药（7.5 μg/kg/inj, i.v）。我们通过(i)将TCP预处理时间从1小时延长至20小时，以及（ii）评估单个TCP立体异构体在尼古丁自我给药研究中的作用，来验证TCP介导的尼古丁自我给药增强是由于MAO抑制还是脱靶效应。而20小时和（−）TCP预处理诱导MAO显著抑制（60-90%），动物发现尼古丁仅微弱增强。此外，（+）和（±）TCP处理均能诱导近100%的MAO抑制，（+）TCP预处理的动物比（±）TCP预处理的动物获得尼古丁自我给药所需的时间更长。（+）TCP预处理动物的稳定尼古丁自我给药受到尼古丁受体激活的影响，但不受尼古丁配对线索的影响。（±）TCP预处理的动物则相反。（−）或（±）TCP处理增加了多巴胺和血清素溢出，而（+）和（±）TCP处理增加了尼古丁后的单胺溢出。总之，我们的数据表明，尼古丁自我给药的tcp增强是通过独立于MAO抑制的机制介导的，包括尼古丁配对线索和单胺摄取抑制。
Our current study aims to evaluate the mechanisms of tranylcypromine (TCP)-mediated enhancement of nicotine self-administration. We replicated our previous findings which demonstrate that 1-hr pretreatment with TCP (3mg/kg, i.p.) enhances nicotine self-administration (7.5 μg/kg/inj, i.v.) when compared with vehicle-treated rodents. We tested whether TCP-mediated enhancement of nicotine self-administration was due to MAO inhibition or off-target effects by (i) extending the TCP pretreatment time from 1 to 20 hr, and (ii) evaluating the role of the individual TCP stereoisomers in nicotine self-administration studies. While 20-hr and (−)TCP pretreatment induced significant inhibition of MAO (60–90%), animals found nicotine only weakly reinforcing. Furthermore, while both (+) and (±)TCP treatment induced nearly 100% MAO inhibition, (+)TCP pretreated animals took longer to acquire nicotine self-administration compared to (±)TCP pretreated animals. Stable nicotine self-administration in (+)TCP pretreated animals was influenced by nicotinic receptor activation but not nicotine-paired cues. The opposite was found in (±)TCP pretreated animals. Treatment with (−) or (±)TCP increased dopamine and serotonin overflow, while the (+) and (±)TCP treatment enhanced monoamine overflow subsequent to nicotine. Together, our data suggests TCP-enhancement of nicotine self-administration are mediated through mechanisms independent of MAO inhibition, including nicotine-paired cues and monoamine uptake inhibition.
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DOI：
10.1021/jm01241a017
发表时间：
1962-01-01
期刊：
JOURNAL OF MEDICINAL & PHARMACEUTICAL CHEMISTRY
影响因子：
--
作者：
KAISER, C;ZIRKLE, CL;DAVIS, CS
通讯作者：
DAVIS, CS
影响因子：
10.6
作者：
Diergaarde, Leontien;Pattij, Tommy;De Vries, Taco J.
通讯作者：
De Vries, Taco J.
影响因子：
3.6
作者：
Di Matteo, V;Cacchio, M;Esposito, E
通讯作者：
Esposito, E
影响因子：
5.8
作者：
FUENTES, JA;OLESHANSKY, MA;NEFF, NH
通讯作者：
NEFF, NH
影响因子：
4.1
作者：
Khalil, AA;Steyn, S;Castagnoli, N
通讯作者：
Castagnoli, N