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1日龄大鼠乙醇强化作用的分析:通过一种简短且新颖的操作性程序进行评估。

Analysis of ethanol reinforcement in 1-day-old rats: assessment through a brief and novel operant procedure.

作者信息

Bordner Kelly A, Molina Juan Carlos, Spear Norman E

机构信息

Center for Developmental Psychobiology, Department of Psychology, Binghamton University-SUNY, Binghamton, New York 13902-600, USA.

出版信息

Alcohol Clin Exp Res. 2008 Apr;32(4):580-92. doi: 10.1111/j.1530-0277.2007.00609.x.

Abstract

BACKGROUND

An accumulating body of experimental evidence supports the notion that, early in development, heterogeneous rats exhibit heightened affinity for ethanol ingestion and are sensitive to the drug's postabsorptive reinforcing effects. The brevity of this ontogenetic period and the limited behavioral repertoire of the newborn represent obstacles in the examination of these phenomena. In the present study, we developed a novel operant technique aimed at examining the neonatal predisposition to gain access to intraoral infusions of different ethanol solutions and other potential reinforcers.

METHODS

In all experiments, 1-day-old rats were placed in a supine position that allowed access to a touch-sensitive sensor. In Paired pups, reinforcers were delivered through an intraoral cannula in a fixed-ratio-1 schedule, based on their physical contact with the sensor. Yoked controls were included to account for overall magnitude of behavioral responding and were given infusions in accord with behavior of the corresponding Paired pup. The reinforcement effect of milk, water and different ethanol solutions (0.75 to 10% v/v) was assessed using a single 15-minute conditioning session. Additional pharmacokinetic studies were conducted to determine blood ethanol concentrations attained during the course of the training session.

RESULTS

Within-subjects analysis revealed that Paired pups rapidly learned to increase the probability of behavioral execution to gain access to a biological reinforcer such as milk (Experiment 1). Follow-up experiments indicated that relatively low ethanol concentrations are equally likely to support operant performance (Experiments 2a and 3a). It was also observed that Paired pups exhibited surprisingly high levels of responding during an extinction session, particularly when initially trained with milk or 3% v/v ethanol as reinforcers (Experiment 4). The pharmacokinetic studies indicated that, within a short period of time, ethanol was detectable in blood. Levels attained during conditioning varied as a function of the ethanol concentration utilized as a reinforcer (Experiments 2b and 3b).

CONCLUSIONS

The present technique appears to represent a valuable tool for examining ethanol self-administration and seeking behavior of the drug during early ontogeny. The results indicate that newborn rats, subjected to the explicit contingency comprising suckling-related behaviors and intraoral ethanol delivery (Paired pups), rapidly learn to gain access to the drug. These results are not explainable through psychomotor effects of ethanol as Yoked pups consumed similar amounts of ethanol and yet exhibited relatively low and consistent levels of responding. The overall pattern of results extends and validates previous observations of substantial affinity for ethanol during early stages of development, a phenomenon rarely encountered in genetically heterogeneous adult rats.

摘要

背景

越来越多的实验证据支持这样一种观点,即在发育早期,异质大鼠对乙醇摄入表现出更高的亲和力,并且对药物吸收后的强化作用敏感。这一发育阶段的短暂性以及新生大鼠有限的行为表现,给研究这些现象带来了障碍。在本研究中,我们开发了一种新颖的操作性技术,旨在研究新生大鼠获取不同乙醇溶液和其他潜在强化物口腔内输注的先天倾向。

方法

在所有实验中,将1日龄大鼠置于仰卧位,使其能够接触到一个触敏传感器。在配对幼崽组中,根据它们与传感器的身体接触,通过口腔插管以固定比例1的程序给予强化物。设置配对对照以考虑行为反应的总体强度,并根据相应配对幼崽的行为给予输注。使用单次15分钟的条件训练来评估牛奶、水和不同乙醇溶液(0.75%至10% v/v)的强化效果。进行了额外的药代动力学研究,以确定训练过程中达到的血液乙醇浓度。

结果

受试者内分析表明,配对幼崽迅速学会增加行为执行的概率,以获取诸如牛奶之类的生物强化物(实验1)。后续实验表明,相对较低的乙醇浓度同样有可能支持操作性表现(实验2a和3a)。还观察到,配对幼崽在消退训练期间表现出惊人的高反应水平,特别是当最初用牛奶或3% v/v乙醇作为强化物进行训练时(实验4)。药代动力学研究表明,在短时间内,血液中可检测到乙醇。训练期间达到的水平因用作强化物的乙醇浓度而异(实验2b和3b)。

结论

本技术似乎是研究乙醇自我给药以及药物在个体发育早期的觅药行为的一种有价值的工具。结果表明,经历了包括与哺乳相关行为和口腔内乙醇递送在内的明确偶联关系的新生大鼠(配对幼崽),迅速学会获取药物。这些结果无法通过乙醇的精神运动效应来解释,因为配对对照幼崽消耗了相似量的乙醇,但表现出相对较低且一致的反应水平。结果的总体模式扩展并验证了先前关于在发育早期对乙醇有显著亲和力的观察结果,这一现象在基因异质的成年大鼠中很少见。

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