Rolipram,a selective phosphodiesterase-4 inhibitor,decreases ethanol seeking and consumption in alcohol-preferring Fawn Hooded rats
作者单位：Howard Florey Institute and Centre for NeuroscienceParkvilleVictoria 3010Australia
会议名称：《中国神经科学学会第九届全国学术会议暨第五次会员代表大会》
会议日期：2011年
学科分类：1002[医学-临床医学] 100205[医学-精神病与精神卫生学] 10[医学]
基 金：supported by the National Nature Science Foundation of China(No30870894) National Basic Research Program of China(No2009CB522000) National Key Technology R&D Program of China(No 2011BAK04B08) supported by the National Health & Medical Research Council,Australia
摘 要：正Alcohol dependence is a complex psychiatric disorder demanding development of novel pharmacotherapy. Since the cyclic AMP（cAMP） signaling cascade has been implicated in mediating the behavioral response to alcohol, it would be of interest to determine whether phosphodiesterase-4（PDE4）,an enzyme that selectively hydrolyzes intracellular cAMP,is involved in the regulation of alcohol ***,the selective PDE4 inhibitor rolipram was used to measure its anti-drinking properties in alcohol-preferring Fawn-Hooded（FH/Wjd） *** showed that acute administration of rolipram（0.05,0.1,and 0.2 mg/kg） selectively and dose-dependently reduced 5%ethanol, but not 10%sucrose,operant self-administration;it also decreased voluntary 5%ethanol intake,but not water consumption,for the initial 30 min in rats showing high stable preference for *** course assessment revealed the significant anti-drinking effect of rolipram（0.1,0.2 mg/kg） lasted for 5 h in both continuous- and intermittentaccess to 5%or 10%***,chronic rolipram treatment decreased 5%ethanol consumption and preference during the drug treatment *** effect lasted even after withdrawal of drug *** locomotor activity was inhibited by rolipram at 0.1 and 0.2 mg/kg,the effect was present only in the initial about 20 min,which did not seem to alter long-term ethanol *** data suggest that PDE4 may play a promising role in ethanol drinking and dependent *** may be a potential treatment target for further development of anti-drinking drugs.