Effects of phosphodiesterase-4 inhibition on alcohol consumption and withdrawal anxiety in Fawn Hooded rats:Evidence for CREB phosphorylation in accumben nucleus core and central amygdala
作者单位：National Institute on Drug DependencePeking University Departments of Behavioral Medicine & Psychiatry and Physiology & PharmacologyWest Virginia University Health Sciences Center
会议名称：《中国神经科学学会第十届全国学术会议》
会议日期：2013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 National Nature Science Foundation of China(30870894) National Basic Research Program of China(2009CB522000) National Key Technology R&D Program of China(2011BAK04B08)
关 键 词：alcohol dependence cyclic AMP signaling phosphodiesterase-4 rolipram FH/Wjd rat
摘 要：Objective Alcohol dependence is a complex psychiatric disorder demanding development of novel *** the cyclic AMP（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 *** 4（PDE4）,an enzyme that specifically catalyzes the hydrolysis of cAMP,represents as a key point in regulating intracellular cAMP ***,it was of interest to determine whether PDE4was involved in the regulation of alcohol use and *** By using Fawn-Hooded（FH/Wjd） rats as the animal model of alcoholism,we tested the effects of rohpram,the specific PDE4 inhibitor,on ethanol intake in two-bottle choice drinking,ethanol self-administration and anxiety symptoms related to ethanol *** molecular analysis was performed to investigate the possible mechanism of rohpram ***（1） Acute administration of rohpram（0.1,0.2 mg/kg,s.c.） selectively reduced ethanol consumption in continuous- and intermittent-access to ethanol at 5%or 10%,respectively;chronic rohpram treatment time-dependently decreased 5%ethanol consumption and preference during treatment days and after the termination of rohpram *** 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 drinking.（2） Rohpram（0.025 mg/kg,0.05 mg/kg,s.c.） dose-dependently inhibited operant self-administration of 5%ethanol,but had no effect on 10%sucrose *** effective dose of rohpram was lower than that of naloxone（0.1 mg/kg）.（3） Anxiety-like behavior was induced following acute ethanol withdrawal after long-time two-bottle choice ***（0.1,0.2 mg/kg,s.c.） significantly reversed this effect by increasing the entries and time spent in the open arms of elevated plus maze（EPM）.（4） cAMP levels in NAc and Amy were