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The Phosphodiesterase-4 (PDE4) Inhibitor Rolipram Decreases Ethanol Seeking and Consumption in Alcohol-Preferring Fawn-Hooded Rats
Wen, Rui-Ting; Zhang, Min; Qin, Wang-Jun; Liu, Qing; Wang, Wei-Ping; Lawrence, Andrew J.2,3; Zhang, Han-Ting4,5; Liang, Jian-Hui1
关键词Camp Signaling Phosphodiesterase-4 Rolipram Fawn-hooded Wjd Rat Etoh Intake
刊名ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
2012-12-01
DOI10.1111/j.1530-0277.2012.01845.x
36期:12页:2157-2167
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Substance Abuse
资助者National Nature Science Foundation of China ; National Basic Research Program of China ; National Key Technology R&amp ; D Program of China ; US NIH/NIAAA ; National Health &amp ; Medical Research Council (Australia) ; National Nature Science Foundation of China ; National Basic Research Program of China ; National Key Technology R&amp ; D Program of China ; US NIH/NIAAA ; National Health &amp ; Medical Research Council (Australia)
研究领域[WOS]Substance Abuse
关键词[WOS]ELEMENT-BINDING PROTEIN ; GENE-TRANSCRIPTION FACTOR ; NUCLEUS-ACCUMBENS ; FH/WJD RAT ; DRINKING BEHAVIOR ; ADDICTION ; CAMP ; CREB ; PHOSPHORYLATION ; ANTIDEPRESSANT
英文摘要

Background Alcohol dependence is a complex psychiatric disorder demanding development of novel pharmacotherapies. Because the cyclic adenosine monophosphate (cAMP) signaling cascade has been implicated in mediating behavioral responses to alcohol, key components in this cascade may serve as potential treatment targets. Phosphodiesterase-4 (PDE4), an enzyme that specifically catalyzes the hydrolysis of cAMP, represents a key point in regulating intracellular cAMP levels. Thus, it was of interest to determine whether PDE4 was involved in the regulation of alcohol use and abuse. Methods Male Fawn-Hooded (FH/Wjd) rats were tested for 5% (v/v) ethanol (EtOH) and 10% (w/v) sucrose operant oral self-administration following treatment with the selective PDE4 inhibitor rolipram (0.0125, 0.025, or 0.05 mg/kg, subcutaneous [s.c.]); rolipram at higher doses (0.05, 0.1, and 0.2 mg/kg, s.c.) was tested to determine its impact on the intake of EtOH, sucrose, or water using the 2-bottle choice drinking paradigm. Subsequent open-field testing was performed to evaluate the influence of higher doses of rolipram on locomotor activity. Results Acute administration of rolipram dose-dependently reduced operant self-administration of 5% EtOH, but had no effect on 10% sucrose responding. Time-course assessment revealed significant decreases in EtOH consumption after rolipram (0.1, 0.2 mg/kg) treatment in continuous- and intermittent access to EtOH at 5% or 10%, respectively. Moreover, chronic rolipram treatment time-dependently decreased 5% EtOH consumption and preference during treatment days and after the termination of rolipram administration. Rolipram at the highest doses (0.1 and 0.2 mg/kg) did decrease locomotor activity, but the effect lasted only 10 and 20 minutes, respectively, which did not likely alter long-term EtOH drinking. Conclusions These results suggest that PDE4 plays a role in alcohol seeking and consumption behavior. Drugs interfering with PDE4 may be a potential pharmacotherapy for alcohol dependence.

语种英语
所属项目编号30870894 ; 2009CB522000 ; 2011BAK04B08 ; AA020042
资助者National Nature Science Foundation of China ; National Basic Research Program of China ; National Key Technology R&amp ; D Program of China ; US NIH/NIAAA ; National Health &amp ; Medical Research Council (Australia) ; National Nature Science Foundation of China ; National Basic Research Program of China ; National Key Technology R&amp ; D Program of China ; US NIH/NIAAA ; National Health &amp ; Medical Research Council (Australia)
WOS记录号WOS:000312131400017
引用统计
被引频次:23[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/54855
专题中国药物依赖性研究所
作者单位1.Univ Melbourne, Ctr Neurosci, Melbourne, Vic, Australia
2.Peking Univ, Natl Inst Drug Dependence, Dept Neuropharmacol, Beijing 100191, Peoples R China
3.Univ Melbourne, Florey Neurosci Inst, Melbourne, Vic, Australia
4.W Virginia Univ, Hlth Sci Ctr, Dept Behav Med & Psychiat, Morgantown, WV 26506 USA
5.W Virginia Univ, Hlth Sci Ctr, Dept Physiol & Pharmacol, Morgantown, WV 26506 USA
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Wen, Rui-Ting,Zhang, Min,Qin, Wang-Jun,et al. The Phosphodiesterase-4 (PDE4) Inhibitor Rolipram Decreases Ethanol Seeking and Consumption in Alcohol-Preferring Fawn-Hooded Rats[J]. ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH,2012,36(12):2157-2167.
APA Wen, Rui-Ting.,Zhang, Min.,Qin, Wang-Jun.,Liu, Qing.,Wang, Wei-Ping.,...&Liang, Jian-Hui.(2012).The Phosphodiesterase-4 (PDE4) Inhibitor Rolipram Decreases Ethanol Seeking and Consumption in Alcohol-Preferring Fawn-Hooded Rats.ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH,36(12),2157-2167.
MLA Wen, Rui-Ting,et al."The Phosphodiesterase-4 (PDE4) Inhibitor Rolipram Decreases Ethanol Seeking and Consumption in Alcohol-Preferring Fawn-Hooded Rats".ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH 36.12(2012):2157-2167.
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