Abstract
The breakpoint (BP) of the progressive ratio (PR) schedule of drug delivery is a commonly used estimate of the drug abuse liability and is interpreted as a measure of motivation to get the next dose. This study investigated BP as a product of the rate of response and the duration of lever-pressing activity. The results were not consistent with the conventional interpretation. Rats were trained to self-administer cocaine intravenously under the fixed ratio (FR1) and PR schedules of delivery. The rate of lever presses and the duration of activity before the last self-injection of different cocaine unit doses and before the last press under the PR schedule were analyzed. The rate of presses was independent of the cocaine unit dose and the duration of activity was proportional to the dose. We assume that BP is a measure of the drug’s overall ability to maintain self-administration under the PR schedule. Therefore, the proportionality between the dose and BP is not evidence of a stronger reinforcing effect of higher doses but the result of cocaine level staying longer within the range of cocaine concentrations (the compulsion zone) capable of inducing lever presses. The relationship between the cocaine unit dose and BP does not represent the dose magnitude of the effect function but the dose duration of the effect function.
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The authors would like to thank Mantana K. Norman for technical assistance.
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This work was supported by the National Institutes of Health grant [DP1DA031386 to A. B. N.].
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V. L. T. wrote software, designed and conducted experiments, analyzed data, and wrote the manuscript; A. B. N. contributed to the idea of the study design, data interpretation and writing of the manuscript, and project administration.
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Tsibulsky, V.L., Norman, A.B. Methodological and analytical issues of progressive ratio schedules: dose duration vs dose magnitude of effect function. Neurosci Behav Physi 52, 778–783 (2022). https://doi.org/10.1007/s11055-022-01282-8
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DOI: https://doi.org/10.1007/s11055-022-01282-8