Reference place conditioning procedure with cocaine: increased sensitivity for measuring associatively motivated choice behavior in rats

Behav Pharmacol. 2010 Jul;21(4):323-31. doi: 10.1097/FBP.0b013e32833b110b.


Place conditioning is widely used to study the conditioned rewarding effects of drugs. In the standard version, one reward (cocaine) is compared with no reward (saline). A modified variant of this task, 'reference-conditioning' procedure, compares two potentially rewarding stimuli (high vs. low cocaine dose). There has been little research on the utility of this procedure. Experiment 1 used the standard protocol with saline administered before confinement to the reference compartment of a place conditioning chamber. On alternate days, saline, 2.5, 5, 7.5, 10, or 20 mg/kg cocaine was administered before confinement to the opposite compartment. In experiments 2 and 3, reference-compartment saline was replaced with 5 and 7.5 mg/kg cocaine, respectively. Relative to saline, 7.5-20 mg/kg cocaine had comparable conditioned rewarding effects (i.e. similar increase in time in paired compartment). When cocaine replaced saline, there was competition at doses lower than 7.5 mg/kg. Rats that received 7.5 versus 2.5 mg/kg spent similar time in each compartment, indicating competition. Competition was not seen with 5 versus 20 mg/kg; preference was for the 20 mg/kg compartment. Experiment 4 showed that the competition at 2.5 mg/kg was not due to reward sensitization. The reference-conditioning procedure has increased the sensitivity for measuring associatively motivated choice behavior.

Publication types

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

MeSH terms

  • Animals
  • Choice Behavior / drug effects*
  • Cocaine / administration & dosage
  • Cocaine / pharmacology*
  • Conditioning, Operant / drug effects*
  • Dose-Response Relationship, Drug
  • Injections, Intraperitoneal
  • Male
  • Motivation*
  • Rats
  • Rats, Sprague-Dawley
  • Reference Standards
  • Reward


  • Cocaine