Expression and Treatment of Pain‐Related Depression of Fixed‐Ratio and Progressive‐Ratio Food‐Maintained Behavior in Rats

Abstract

Pain‐related interference with behavior is a key clinical diagnostic indicator and target in the treatment of pain. Increasingly, preclinical studies on the expression, mechanisms, and treatment of pain have been aimed at improving understanding of pain‐related interference with behavior. Positively reinforced operant behavior is one category of target behaviors that are sensitive to depression by physiologically‐relevant pain stimuli. This pain‐related depression of behavior can be blocked by clinically‐effective analgesics including opioids and nonsteroidal anti‐inflammatory drugs. Most studies using operant conditioning procedures to examine pain‐related depression of behavior have used fixed‐ratio schedules of reinforcement. The primary dependent variable in these studies is the rate of behavior. In contrast, the primary dependent variable in studies using progressive ratio schedules of reinforcement is breakpoint. Breakpoint is often defined as the final ratio completed by the subject or total number of reinforcers earned, and is thought to be related to the efficacy of the reinforcer or the subject's motivation to obtain the reinforcer. The present studies compare the effects of a noxious pain stimulus and a clinically‐relevant analgesic on behavior maintained under fixed‐ratio and progressive‐ratio schedules of behavior in male Wistar rats. The first aim was to determine whether there were differences in the potency of an acute chemical noxious stimulus, intraperitoneal injection of dilute lactic acid, to depress operant behavior maintained by sucrose under fixed‐ and progressive‐ratio schedules of reinforcement. Under the fixed‐ratio schedule, rats were required to perform six lever presses to access 0.1 ml of 10% sucrose, under the progressive‐ratio schedule, the response requirement increased following the delivery of each reinforcer according to a logarithmic function. Lactic acid was more potent at depressing lever pressing under the fixed‐ratio schedule compared to the progressive‐ratio schedule. The second aim of the study was to examine the effects of the NSAID, ketoprofen, on lactic acid‐induced depression of lever pressing. Consistent with previous studies, ketoprofen was effective at blocking pain‐related depression of behavior maintained under both fixed‐ and progressive‐ratio schedules, and ketoprofen was equipotent in both procedures. Together, these findings support the validity of operant procedures as tools to examine candidate analgesics for the treatment of pain‐related depression of behavior. Moreover, the use of diverse schedules of reinforcement may yield important scientific information on the mechanisms underlying pain‐related interference with behavior. Specifically, the finding that, under the current experimental conditions, lactic acid was more potent to depress lever pressing maintained under a fixed‐ratio schedule than a progressive‐ratio schedule may reflect interference with the rats' ability to respond at a high rate at concentrations that did not impact their motivation to do so.Support or Funding InformationSupported by a University of Georgia‐Augusta University (AU) seed grant, the AU Center for Undergraduate Research and Scholarship, and the AU College of Science and Mathematics.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.