Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA.
Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA.
J Neurosci Methods. 2021 May 15;356:109146. doi: 10.1016/j.jneumeth.2021.109146. Epub 2021 Mar 23.
The break point (BP) of the progressive ratio (PR) schedule of drug delivery is a well-recognized parameter in self-administration studies. Nonetheless, two problems remain unresolved: there is no rationally justified criterion for the last response at BP; the both commonly used definitions of BP as the number of deliveries or the last complete progressive ratio requirement are not the best assuming that BP is a measure of motivation.
A criterion for the last lever press is proposed in this study using intravenous cocaine self-administration in rats. The rationale is based on the finding that long inter-press intervals have initially very low probability to occur during the self-administration phase of the session under the PR schedule. But this probability dramatically increases when inter-injection intervals increase due to high ratio requirements.
For cocaine these critical inter-press intervals were 7.5 min and longer. This novel criterion was applied to measure BP according to all four theoretically plausible definitions of BP including the new one: the higher of the two numbers of presses before or after the last delivery of the reinforcer.
The conventionally defined BP is significantly lower (by 12 %) than BP defined according to the new proposed definition. The new definition of BP provides not only a more accurate value of BP but now the variance of BP at different cocaine doses is homogeneous as required by many statistical tests.
These new definitions of the last press and BP provide more accurate and statistically homogenous measure of BP.
递增比率（PR）给药方案的断点（BP）是自我给药研究中公认的参数。尽管如此，仍有两个问题尚未解决：BP 最后一次反应没有合理的判断标准；BP 作为给药次数或最后完整递增比率要求的两种常用定义并不最佳，因为 BP 是动机的衡量标准。
本研究使用大鼠静脉可卡因自我给药，提出了 BP 最后一次 lever press 的判断标准。其基本原理是基于这样的发现，即在 PR 方案的自我给药阶段，长时间的按压间隔最初出现的概率非常低。但由于高比率要求，当注射间隔增加时，这种概率会显著增加。
对于可卡因，这些关键的按压间隔为 7.5 分钟及更长。该新方法应用于根据包括新定义在内的 BP 的四种理论上合理的定义来测量 BP：在最后一次强化物给药之前或之后按压次数较高的那两个数。
根据传统定义的 BP 显著低于（低 12%）根据新提出的定义定义的 BP。BP 的新定义不仅提供了更准确的 BP 值，而且现在，根据许多统计检验的要求，不同可卡因剂量下的 BP 方差是均匀的。
这些新的最后一次按压和 BP 定义提供了更准确和统计学上均匀的 BP 测量方法。
