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Assessment of the effects of contingent histamine injections on the reinforcing effectiveness of cocaine using behavioral economic and progressive-ratio designs.

Psychopharmacology (2014-01-09)
Kevin B Freeman, Brian C McMaster, Peter G Roma, William L Woolverton
ABSTRACT

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. 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. 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. 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. 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).

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Histamine dihydrochloride, ≥99% (TLC), powder
Sigma-Aldrich
Cocaine hydrochloride
Sigma-Aldrich
Histamine dihydrochloride, ≥99.0% (AT)
Supelco
Cocaine hydrochloride solution, 1.0 mg/mL in methanol, analytical standard, for drug analysis
Histamine dihydrochloride, European Pharmacopoeia (EP) Reference Standard