Kevin B Freeman1, Brian C McMaster, Peter G Roma, William L Woolverton. 1. Division of Neurobiology and Behavior Research, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, 39216, USA, kfreeman@umc.edu.
Abstract
RATIONALE: Recent research has demonstrated that the drug, histamine, can function as a punisher of cocaine self-administration. However, little is known about how drug punishers affect the maximum reinforcing effectiveness of drugs as reinforcers. OBJECTIVE: The goal of the present study was to determine if histamine, when self-administered as a mixture with cocaine, could reduce cocaine's maximum reinforcing effectiveness using two procedures designed for measuring reinforcing effectiveness. METHODS: In the first experiment, rhesus monkeys were allowed to self-administer cocaine (0.1 mg/kg/inj) alone or as a mixture with histamine (0.012-0.05 mg/kg/inj) in a behavioral economic design. In the second experiment, monkeys were allowed to self-administer cocaine alone (0.006-0.56 mg/kg/inj) or as a mixture with histamine (0.025-0.1 mg/kg/inj) under a progressive-ratio schedule of reinforcement. RESULTS: In Experiment 1, histamine decreased the reinforcing effectiveness of cocaine in a dose-dependent manner as evidenced by increases in cocaine's demand elasticity with increases in histamine dose. In Experiment 2, histamine decreased cocaine's potency and effectiveness as a reinforcer in a dose-dependent manner as indicated by rightward and downward shifts, respectively, in the dose-response functions. CONCLUSION: The reinforcing effectiveness of cocaine can be reduced by contingent self-administration of histamine. These results indicate that combining drug punishers with drug reinforcers reduces the maximum reinforcing effect of the drug reinforcer, which suggests a use for drug punishers as a deterrent to drug abuse (e.g., as mixtures with prescription medications with abuse potential).
RATIONALE: Recent research has demonstrated that the drug, histamine, can function as a punisher of cocaine self-administration. However, little is known about how drug punishers affect the maximum reinforcing effectiveness of drugs as reinforcers. OBJECTIVE: The goal of the present study was to determine if histamine, when self-administered as a mixture with cocaine, could reduce cocaine's maximum reinforcing effectiveness using two procedures designed for measuring reinforcing effectiveness. METHODS: In the first experiment, rhesus monkeys were allowed to self-administer cocaine (0.1 mg/kg/inj) alone or as a mixture with histamine (0.012-0.05 mg/kg/inj) in a behavioral economic design. In the second experiment, monkeys were allowed to self-administer cocaine alone (0.006-0.56 mg/kg/inj) or as a mixture with histamine (0.025-0.1 mg/kg/inj) under a progressive-ratio schedule of reinforcement. RESULTS: In Experiment 1, histamine decreased the reinforcing effectiveness of cocaine in a dose-dependent manner as evidenced by increases in cocaine's demand elasticity with increases in histamine dose. In Experiment 2, histamine decreased cocaine's potency and effectiveness as a reinforcer in a dose-dependent manner as indicated by rightward and downward shifts, respectively, in the dose-response functions. CONCLUSION: The reinforcing effectiveness of cocaine can be reduced by contingent self-administration of histamine. These results indicate that combining drug punishers with drug reinforcers reduces the maximum reinforcing effect of the drug reinforcer, which suggests a use for drug punishers as a deterrent to drug abuse (e.g., as mixtures with prescription medications with abuse potential).
Authors: C Austin Zamarripa; Jennifer E Naylor; Sally L Huskinson; E Andrew Townsend; Thomas E Prisinzano; Kevin B Freeman Journal: Psychopharmacology (Berl) Date: 2020-01-31 Impact factor: 4.530