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

Abstract

BackgroundThe 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. New MethodA 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. ResultsFor 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. Comparison with Existing MethodThe 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. ConclusionThese new definitions of the last press and BP provide more accurate and statistically homogenous measure of BP.