Vladimir L Tsibulsky1, Andrew B Norman2. 1. Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA. Electronic address: vladimir.tsibulsky@uc.edu. 2. Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA.
Abstract
BACKGROUND: 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. NEW METHOD: 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. RESULTS: 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. COMPARISON WITH EXISTING METHOD: 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. CONCLUSION: These new definitions of the last press and BP provide more accurate and statistically homogenous measure of BP.
BACKGROUND: 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. NEW METHOD: 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. RESULTS: 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. COMPARISON WITH EXISTING METHOD: 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. CONCLUSION: These new definitions of the last press and BP provide more accurate and statistically homogenous measure of BP.