Cocaine self-administration and reinstatement in female rats selectively bred for high and low voluntary running

Drug Alcohol Depend. 2016 Oct 1;167:163-8. doi: 10.1016/j.drugalcdep.2016.08.020. Epub 2016 Aug 21.


Background: Previous research has found that rats behaviorally screened for high (vs. low) wheel running were more vulnerable to cocaine abuse. To assess the extent to which a genetic component is involved in this drug-abuse vulnerability, rats selectively bred for high or low voluntary running (HVR or LVR, respectively) were examined for differences in cocaine seeking in the present study.

Methods: Female rats were trained to lever press for food and then were assessed for differences in acquisition of cocaine (0.4mg/kg; i.v.) self-administration across 10 sessions. Once acquired, rats self-administered cocaine for a 14-day maintenance phase, followed by a 14-day extinction phase when cocaine was no longer available. Subsequently, reinstatement of cocaine seeking was examined with priming injections of cocaine (5, 10 & 15mg/kg), caffeine (30mg/kg), yohimbine (2.5mg/kg) and cocaine-paired cues.

Results: A greater percentage of LVR rats met the acquisition criteria for cocaine self-administration and in fewer sessions than HVR rats. No differences in responding for cocaine were observed between phenotypes during maintenance. However, during extinction LVR rats initially responded at higher rates and persisted in cocaine seeking for a greater number of sessions. No phenotype differences were observed following drug and cue-primed reinstatement of cocaine seeking.

Conclusions: In general, LVR rats were more sensitive to the reinforcing effects of cocaine than HVR rats during periods of transition into and out of cocaine self-administration. Thus, LVR rats sometimes showed a greater vulnerability cocaine seeking than HVR rats.

Keywords: Acquisition; Cocaine self-administration; Extinction; Phenotype; Rats; Wheel running.

MeSH terms

  • Adrenergic alpha-2 Receptor Antagonists / pharmacology
  • Animals
  • Caffeine / pharmacology
  • Central Nervous System Stimulants / administration & dosage*
  • Cocaine / administration & dosage*
  • Cocaine-Related Disorders / physiopathology
  • Cues
  • Extinction, Psychological / drug effects*
  • Female
  • Motor Activity / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Reinforcement, Psychology*
  • Running
  • Self Administration*
  • Yohimbine / pharmacology


  • Adrenergic alpha-2 Receptor Antagonists
  • Central Nervous System Stimulants
  • Yohimbine
  • Caffeine
  • Cocaine