Demand for Methamphetamine and Methcathinone Under Fixed Ratio and Second‐Order Schedules of Reinforcement

Abstract

Behavioral economic procedures, e.g., demand curve analysis, provide powerful quantitative metrics for scaling the strength of drugs of abuse. Most studies that have utilized such procedures employ simple fixed ratio (FR) schedules of reinforcement to generate demand curves. However, second‐order schedules, in which a subject responds under one schedule of conditioned reinforcement (e.g., for presentation of a brief light stimulus) that is nested within a second schedule of primary reinforcement, have been suggested to more accurately reflect the complex patterns of behavior that accompany human drug taking. Further, the conditioned stimulus presented during second order schedules may develop conditioned reinforcer properties that serve to maintain drug‐taking behavior in their own right. The objective of the present study was to begin to compare self‐administration and demand for intravenous methamphetamine and methcathinone under both simple FR and second‐order schedules of reinforcement in nonhuman primates. Adult male squirrel monkeys (N=4) with histories of stimulant self‐administration responded for intravenous methamphetamine and methcathinone injections under FR10 and FR10(FR5:S) schedules of reinforcement. After self‐administration of vehicle and a range of methamphetamine (0.001–0.1 mg/kg) and methcathinone (0.001–0.1 mg/kg) doses were evaluated under each schedule, two doses of each drug (0.01 and 0.03 mg/kg/inj) were studied using a demand procedure; for the FR condition, the response requirement for drug delivery increased across multiple sessions in an ascending order, i.e. FR 10, 30, 56, 100, etc. For the second‐order condition, the response requirement for the drug delivery schedule increased according to a similar progression (i.e., FR10(FR5:S), FR30(FR5:S), FR56(FR5:S), etc.). Each condition was presented in a random order that was counterbalanced across subjects. Results indicate that methamphetamine and methcathinone self‐administration followed an inverted‐U shaped pattern with similar total intake (mg/kg) under the two schedules of reinforcement. During demand procedures, both methamphetamine and methcathinone self‐administration gradually decreased as the response requirement was increased. Application of the exponential model of demand shows that the higher dose of methamphetamine (0.03 mg/kg) produced slightly greater breakpoints than the lower dose (0.01 mg/kg) under both schedule conditions whereas demand for methcathinone was generally higher under FR than second‐order schedules regardless of dose. Interestingly, demand for the high doses of the two drugs was less elastic under the FR condition, whereas demand for the lower doses was more elastic under the second‐order schedule. These results suggest that the demand for self‐administered drugs may be influenced by schedule of reinforcement in a manner that varies across drugs. Further, the present results do not support a facilitative influence of conditioned reinforcement on the reinforcing strength of self‐administered drugs.Support or Funding InformationThis work was funded by National Institutes of Health grants DA002519 and DA039306This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.