Separate measures of ethanol seeking and drinking in the rat: effects of remoxipride

Separate measures of ethanol seeking and drinking in the rat: effects of remoxipride
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DOI:
10.1016/s0741-8329(02)00236-7
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发表时间:
2002-08-01
期刊:
影响因子:
2.3
通讯作者:
Samson, HH
Samson, HH
中科院分区:
医学4区
文献类型:
--
作者:
Czachowski, CL;Santini, LA;Samson, HH

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RemoxiPride是一种多巴胺D-2拮抗剂,它减少了导致在有限进入范例中出现少量(类似于0.1毫升)乙醇的反应。这种类型的操作性反应是一种组合的食欲/消耗性反应,在治疗过程中受到所消费乙醇的刺激性质(即味道、药理)的不同影响。在目前的实验设计中,酒精引导的食欲反应和消耗性反应被程序性地分离,以研究RemxiPride对这些不同行为的具体影响。雄性Long-Evans大鼠每天训练一次杠杆按压反应,使其接触含有10%乙醇的吸管喷嘴20分钟。试验分三个剂量:5.0、10.0和15.0 mg/kg(-30min,i.p.)。在实验1中,使用了20的反应要求,并检查了强化和非强化会话。在非强化训练中,受试者被允许杠杆按压20分钟,之后训练结束,不会出现吸管。进行这些会话是为了排除限制反应可能会掩盖寻求反应中的药物效应的可能性。在实验2中,采用低反应要求(4)来研究雷米昔普利对乙醇摄入量的影响。平均基础酒精摄入量(实验1)为0.69g/kg,训练结束时血中乙醇浓度为mg%。在测试的所有剂量下,REMOXPRIE对两个实验中的酒精消耗指标(例如,总摄入量、舔唇潜伏期、舔舌率)都没有影响。然而,在实验1中,在强化和非强化过程中,REMOXPRIE剂量依赖性地减少了食欲反应的次数,而对反应潜伏期或反应速度没有影响。在这些实验中,多巴胺D2受体的全身拮抗减少了酒精寻求,而不会导致运动功能的普遍损害。寻求反应和摄取反应的程序性分离表明,食欲反应比消耗性反应对REMOXPRIE治疗更敏感。(C)2002 Elsevier Science Inc.保留所有权利。
Remoxipride, a dopamine D-2 antagonist, decreases responding that results in the presentation of small amounts (similar to0.1 ml) of ethanol in limited-access paradigms. This type of operant response is a combined appetitive/consummatory response that is differentially affected by changing stimulus properties of consumed ethanol (i.e., taste, pharmacology) over the course of the session. In the present experimental design, ethanol-directed appetitive and consummatory responses were procedurally separated to investigate the specific effects of remoxipride on these distinct behaviors. Male Long-Evans rats were trained to make a series of lever-press responses once each day that resulted in access to a sipper tube spout containing 10% ethanol for 20 min. Three doses of remoxipride were tested: 5.0, 10.0, and 15.0 mg/kg (-30 min, i.p.). In Experiment 1, a response requirement of 20 was used, and both reinforced and nonreinforced sessions were examined. In nonreinforced sessions, subjects were permitted to lever press for 20 min, after which the session ended without sipper tube presentation. These sessions were conducted to remove the possibility that limiting responding might obscure a drug effect on the seeking response. In Experiment 2, a low response requirement (4) was used to investigate the effects of remoxipride on ethanol intake. Average baseline ethanol intake (Experiment 1) was 0.69 g/kg, with blood ethanol concentrations at the end of the session at 64 mg%. At all doses tested, remoxipride had no effect on the measures of ethanol consumption (e.g., total intake, lick latency, lick rate) in either experiment. However, remoxipride dose dependently decreased the number of appetitive responses made, while having no effect on response latency or rate, during both reinforced and nonreinforced sessions in Experiment 1. In these experiments, the systemic antagonism of the dopamine D2 receptor decreased ethanol seeking without causing a general impairment of motor function. The procedural separation of seeking and intake responses revealed that appetitive responding was more sensitive than consummatory responding to remoxipride treatment. (C) 2002 Elsevier Science Inc. All rights reserved.