Methodological and analytical issues of progressive ratio schedules: Definition and scaling of breakpoint

• Published in: Journal of neuroscience methods 2021-05, Vol.356, p.109146-109146, Article 109146
• Main Authors: Tsibulsky, Vladimir L., Norman, Andrew B.
• Format: Article
• Language: English
• Subjects: Animals; Breakpoint; Cocaine; Definitions; Dose-Response Relationship, Drug; Drug addiction; Inter-press intervals; Motivation; Progressive ratio schedule; Rats; Reinforcement Schedule; Self Administration
• ISSN: 0165-0270; 1872-678X; 1872-678X
• DOI: 10.1016/j.jneumeth.2021.109146

•The progressive-ratio method requires a definition of the last lever press followed by remission.•The proposed definition is based on a critical inter-press interval.•BP is redefined as the greater of two numbers: the last complete ratio requirement or the number of presses between the last injection and last press.•New breakpoint values satisfy the requirement of homogeneity between doses. 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.