Effects of β-adrenoceptor antagonists on alcohol drinking by alcohol-dependent rats
Effects of β-adrenoceptor antagonists on alcohol drinking by alcohol-dependent rats
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DOI：
10.1007/s00213-010-1967-8
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发表时间：
2010-10-01
影响因子：
3.4
通讯作者：
Koob, George F.
中科院分区：
文献类型：
--
作者：
Gilpin, Nicholas W.;Koob, George F.
酒精依赖动物在酒精戒断过程中表现出增强的应激反应、奖赏阈值和酒精自我给药，其中一些酒精依赖的方面可能是由脑去甲肾上腺素（NE）系统的激活介导的。在酒精依赖和非酒精依赖大鼠的操作性酒精强化反应。成年雄性Wistar大鼠被训练在一个操作性条件反射范式中对酒精的反应，比率-1（FR-1）和累进比率（PR）加固计划。大鼠通过慢性间歇性（14小时开/10小时关）酒精蒸汽吸入依赖酒精或不暴露于酒精蒸汽。在大鼠戒断6- 8h的时间点，观察普萘洛尔（0-10 mg/kg）或纳多洛尔（0-20 mg/kg）对酒精依赖大鼠FR-1操作性酒精增强反应的影响，发现普萘洛尔各剂量均抑制酒精依赖大鼠的FR-1操作性酒精增强反应，但仅最高剂量抑制对照大鼠的FR-1反应。不同剂量普萘洛尔对水反应无影响。纳多洛尔不影响操作行为。普萘洛尔抑制PR操作性酒精强化反应各组，效果归因于酒精反应的显着抑制在最高dose. After酒精依赖的发展，大鼠表现出超敏反应普萘洛尔对操作性酒精强化反应的抑制作用。这种作用是由药物的中枢作用介导的，不归因于运动效应，可能反映了大脑NE系统的激活，这有助于戒断诱导的负面情绪状态，并促使依赖生物体饮酒。
Alcohol-dependent animals display enhanced stress responsivity, reward thresholds, and alcohol self-administration during alcohol withdrawal, and some of these aspects of alcohol dependence may be mediated by activation of brain norepinephrine (NE) systems.This study examined the effects of propranolol, a beta-adrenoceptor antagonist, on operant alcohol-reinforced responding by alcohol-dependent and non-dependent rats.Adult male Wistar rats were trained to respond for alcohol in an operant conditioning paradigm on fixed-ratio-1 (FR-1) and progressive ratio (PR) reinforcement schedules. Rats were either made dependent on alcohol via chronic intermittent (14 h ON/10 h OFF) alcohol vapor inhalation or were not exposed to alcohol vapor. Rats were tested for the effects of propranolol (0-10 mg/kg) or nadolol (0-20 mg/kg) on operant alcohol-reinforced responding at the time point corresponding to 6-8 h withdrawal in dependent animals.All doses of propranolol suppressed FR-1 operant alcohol-reinforced responding in alcohol-dependent rats, but only the highest dose suppressed FR-1 responding by controls. No dose of propranolol affected water responding. Nadolol did not affect operant behavior. Propranolol suppressed PR operant alcohol-reinforced responding across groups, an effect attributable to significant suppression of alcohol responding at the highest dose.Following development of alcohol dependence, rats exhibit hypersensitivity to the suppressive effects of propranolol on operant alcohol-reinforced responding. This effect is mediated by central actions of the drug, is not attributable to motor effects, and may reflect activation of brain NE systems that contributes to withdrawal-induced negative emotional states and drives alcohol drinking in the dependent organism.