Czachowski C L, Samson H H
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1083, USA.
Alcohol Clin Exp Res. 1999 Oct;23(10):1580-6.
Progressive ratio schedules are used to determine the "breakpoint" or limit to the amount of "work" that a subject is willing to perform to obtain a reinforcer. Reinforcing efficacy is inferred from the breakpoint values, which are typically measured in a single session by increasing the number of responses required for successive reinforcer presentations. This procedure is not feasible, however, when assessing the reinforcing efficacy of a substance that can change as a function of its physiological actions during self-administration, as in the case of ethanol.
The present study made use of a procedure that increased the response requirement across single daily sessions rather than within a session. Completion of the response requirement in each daily session resulted in the presentation of a drinking tube that allowed for self-administration of ethanol for a 20-min period. This procedure made possible the assessment of ethanol-directed appetitive (number of lever presses) and consummatory (number of licks and intake volume) behaviors. Reliable responding for 10% ethanol was initiated using sucrose-substitution on a fixed ratio (FR) 4 schedule in male Long Evans rats. Then four successive breakpoint determinations were made which were separated by a return to the FR4 schedule to re-establish baseline responding.
The results indicated that there was an increase in breakpoint values from the first to the second determination, which was then stable over the following three determinations. Individual rats reached breakpoints as high as 240 lever presses to receive access to 10% ethanol and maintained ethanol intake over sessions in the 1.0 g/kg range. Ethanol intake (g/kg), however, was stable across all four determinations (mean 0.86 +/- 0.06 to 1.01 +/- 0.10). Moreover, ethanol intake was not related to the preceding appetitive responding, as no differences between intake on the session before a breakpoint (high FR) and the following baseline period (FR4) were observed.
This model provides an assessment of the distinct mechanisms that mediate ethanol-seeking versus ethanol consumption in subjects that drink measurable amounts of ethanol, with the appetitive behaviors not altered by the pharmacological effects of ethanol.
累进比率程序用于确定被试为获得强化物而愿意执行的“工作量”的“断点”或限度。强化效能是从断点值推断出来的,断点值通常在单个实验中通过增加连续呈现强化物所需的反应次数来测量。然而,当评估一种物质的强化效能时,这种程序是不可行的,因为该物质的强化效能可能会随着其在自我给药过程中的生理作用而变化,乙醇就是这种情况。
本研究采用了一种在每日单次实验中增加反应要求而不是在一次实验内增加反应要求的程序。在每个每日实验中完成反应要求会导致出现一个饮水管,允许在20分钟内自我给予乙醇。这个程序使得评估针对乙醇的欲求行为(杠杆按压次数)和 consummatory行为(舔舐次数和摄入量)成为可能。在雄性长 Evans 大鼠中,使用蔗糖替代物在固定比率(FR)4程序上启动对10%乙醇的可靠反应。然后进行了四次连续的断点测定,每次测定之间通过回到FR4程序来重新建立基线反应。
结果表明,从第一次测定到第二次测定,断点值有所增加,然后在接下来的三次测定中保持稳定。个别大鼠达到高达240次杠杆按压的断点以获得10%乙醇的摄入机会,并在各实验中保持乙醇摄入量在1.0 g/kg范围内。然而,乙醇摄入量(g/kg)在所有四次测定中是稳定的(平均值为0.86±0.06至1.01±0.10)。此外,乙醇摄入量与之前的欲求反应无关,因为在断点前的实验(高FR)和随后的基线期(FR4)的摄入量之间未观察到差异。
该模型提供了对介导可测量乙醇摄入量的个体中寻求乙醇与消耗乙醇的不同机制的评估,其中欲求行为不受乙醇药理作用的影响。