Phosphodiesterase-4 inhibitor rolipram decreases ethanol seeking and consumption in alcohol-preferring fawn-hooded rats
作者单位：Florey Neuroscience Institutes and Centre for NeuroscienceUniversity of MelbourneVictoriaAustralia
会议名称：《中国药理学会第十一次全国学术会议》
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：The project supported by National Natural Science Foundation of China(30870894) National Basic Research Program of China (2009CB522000) National Key Technology R&D Program of China(2011BAK04B08) US NIH-/NIAAA(AA020042) the National Health & Medical Research Council(Australia)
关 键 词：cyclic AMP signaling phosphodiesterase-4 rolipram FH/Wjd rat ethanol intake
摘 要：OBJECTIVE Since cyclic AMP(cAMP) signaling cascade has been implicated in mediating behavioral responses to alcohol, key components in this cascade may serve as potential treatment *** 4(PDE4),an enzyme that specifically catalyzes the hydrolysis of cAMP,plays a critical role in regulating its intracellular ***,it was of interest to determine whether PDE4 was involved in the regulation of alcohol use and *** Male Fawn-Hooded(FH/Wjd) rats were tested for 5%(V/V) ethanol and 10%(W/V) sucrose operant oral self-administration following treatment with the selective PDE4 inhibitor rolipram(0.0125,0.025,and 0.05 mg·kg,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 ethanol,sucrose,or water using the two-botde choice drinking *** open-field testing was performed to evaluate the influence of higher doses of rolipram on locomotor *** Acute administration of rolipram dose-dependently reduced operant self-administration of 5%ethanol,but had no effect on 10%sucrose ***-course assessment revealed a significant anti-drinking effect of rolipram(0.1 and 0.2 mg·kg) in continuous-and intermittent-access to ethanol at 5%or 10%,***,chronic rolipram treatment time-dependently decreased 5%ethanol consumption and preference during treatment days and after the termination of rolipram *** at the highest doses(0.1 and 0.2 mg·kg) did decrease locomotor activity,but the effect lasted only 10 and 20 min,respectively,which did not likely alter long-term ethanol *** These results suggest that PDE4 plays a role in alcohol seeking and consumption *** interfering with PDE4 may be a potential pharmacotherapy for alcohol dependence.