A generalized matching law analysis of cocaine vs. food choice in rhesus monkeys: effects of candidate 'agonist-based' medications on sensitivity to reinforcement

Drug Alcohol Depend. 2015 Jan 1:146:52-60. doi: 10.1016/j.drugalcdep.2014.11.003. Epub 2014 Nov 20.

Abstract

Background: We have previously demonstrated reductions in cocaine choice produced by either continuous 14-day phendimetrazine and d-amphetamine treatment or removing cocaine availability under a cocaine vs. food choice procedure in rhesus monkeys. The aim of the present investigation was to apply the concatenated generalized matching law (GML) to cocaine vs. food choice dose-effect functions incorporating sensitivity to both the relative magnitude and price of each reinforcer. Our goal was to determine potential behavioral mechanisms underlying pharmacological treatment efficacy to decrease cocaine choice.

Methods: A multi-model comparison approach was used to characterize dose- and time-course effects of both pharmacological and environmental manipulations on sensitivity to reinforcement.

Results: GML models provided an excellent fit of the cocaine choice dose-effect functions in individual monkeys. Reductions in cocaine choice by both pharmacological and environmental manipulations were principally produced by systematic decreases in sensitivity to reinforcer price and non-systematic changes in sensitivity to reinforcer magnitude.

Conclusions: The modeling approach used provides a theoretical link between the experimental analysis of choice and pharmacological treatments being evaluated as candidate 'agonist-based' medications for cocaine addiction. The analysis suggests that monoamine releaser treatment efficacy to decrease cocaine choice was mediated by selectively increasing the relative price of cocaine. Overall, the net behavioral effect of these pharmacological treatments was to increase substitutability of food pellets, a nondrug reinforcer, for cocaine.

Keywords: Choice, Rhesus monkey; Cocaine; Generalized matching law; Monoamine releaser; Sensitivity to reinforcement.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Choice Behavior / drug effects*
  • Cocaine / administration & dosage*
  • Cocaine / pharmacology
  • Conditioning, Operant / drug effects
  • Dextroamphetamine / pharmacology*
  • Dose-Response Relationship, Drug
  • Food*
  • Macaca mulatta
  • Male
  • Models, Psychological
  • Morpholines / pharmacology*
  • Phenmetrazine / pharmacology*
  • Reinforcement, Psychology*
  • Self Administration

Substances

  • Morpholines
  • phendimetrazine
  • Cocaine
  • Dextroamphetamine
  • Phenmetrazine