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氟伏沙明对两种大鼠品系中乙醇和食物维持行为多重模式的影响。

Effects of fluvoxamine on a multiple schedule of ethanol- and food-maintained behavior in two rat strains.

作者信息

Ginsburg Brett C, Koek Wouter, Javors Martin A, Lamb R J

机构信息

Department of Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78228, USA.

出版信息

Psychopharmacology (Berl). 2005 Jul;180(2):249-57. doi: 10.1007/s00213-005-2156-z. Epub 2005 Jan 29.

Abstract

RATIONALE

Previous studies show that selective serotonin reuptake inhibitors (SSRIs), including fluvoxamine, have a greater effect on ethanol-maintained responding compared with an alternative reinforcer. However, none of these studies matched baseline responding for reinforcers. Because behavioral effects of many drugs depend on the baseline response rate, the preferential effects of SSRIs may be due to different baseline response rates.

OBJECTIVES

Fluvoxamine effects on ethanol- and food-maintained responding were compared using a multiple schedule of behavior, providing matched baseline responding and allowing within-subject analysis in two strains of rats.

METHODS

The multiple schedule consisted of three consecutive 5-min, fixed-ratio five components (Food1, Ethanol, Food2). Fluvoxamine (3-30 mg/kg, i.p.) was administered 30 min presession. In Lewis rats, fluvoxamine effects were determined at several available ethanol concentrations [8, 16, 32, and 8% (w/v) redetermination]. In Sprague-Dawley rats, fluvoxamine effects were determined when the available ethanol concentration was 8% (w/v).

RESULTS

Baseline responding was stable and well matched under all conditions except 32% ethanol, when responding for ethanol was lower than for food. After the administration of 17.8 mg/kg fluvoxamine, ethanol-maintained responding was 15-33% lower than food-maintained responding in four of the five conditions tested. Breath ethanol assessments indicated that rats had blood ethanol levels of 33 mg/dl following responding for 8% ethanol.

CONCLUSIONS

These results are in agreement with previous findings that SSRIs preferentially reduce ethanol-maintained responding and suggest this is not likely due to different baseline levels of responding between the comparison conditions. Further, these results support the hypothesis that alteration of synaptic serotonin can modulate ethanol reinforcement.

摘要

原理

先前的研究表明,包括氟伏沙明在内的选择性5-羟色胺再摄取抑制剂(SSRI)相较于其他强化物,对乙醇维持的反应有更大影响。然而,这些研究均未使强化物的基线反应相匹配。由于许多药物的行为效应取决于基线反应率,SSRI的优先效应可能归因于不同的基线反应率。

目的

使用多重行为程序比较氟伏沙明对乙醇和食物维持反应的影响,提供匹配的基线反应,并允许在两种品系的大鼠中进行个体内分析。

方法

多重程序由三个连续的5分钟固定比率为5的成分组成(食物1、乙醇、食物2)。在实验前30分钟腹腔注射氟伏沙明(3 - 30毫克/千克)。在刘易斯大鼠中,在几种可用的乙醇浓度[8%、16%、32%和8%(重量/体积)重新测定]下确定氟伏沙明的效果。在斯普拉格-道利大鼠中,当可用乙醇浓度为8%(重量/体积)时确定氟伏沙明的效果。

结果

除了32%乙醇的情况外,在所有条件下基线反应都稳定且匹配良好,此时对乙醇的反应低于对食物的反应。在注射17.8毫克/千克氟伏沙明后,在测试的五种条件中的四种条件下,乙醇维持的反应比食物维持的反应低15% - 33%。呼气乙醇评估表明,大鼠在对8%乙醇做出反应后血液乙醇水平为33毫克/分升。

结论

这些结果与先前的发现一致,即SSRI优先降低乙醇维持的反应,并表明这不太可能是由于比较条件之间不同的基线反应水平所致。此外,这些结果支持突触5-羟色胺的改变可调节乙醇强化作用的假说。

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