Contributions of Prolonged Contingent and Noncontingent Cocaine Exposure to Enhanced Reinstatement of Cocaine Seeking in Rats

Psychopharmacology (Berl). 2006 Jul;187(1):60-7. doi: 10.1007/s00213-006-0386-3. Epub 2006 Apr 6.


Rationale: Recent evidence suggests that prolonged cocaine self-administration produces escalation in drug-seeking behavior in rats analogous to the increased intake patterns observed in cocaine-dependent individuals. However, the contributions of prolonged access to cocaine taking vs the pharmacologic effects of the consequent increased cocaine exposure on escalation of drug-seeking behaviors have not been investigated.

Objective: The present study assessed the effects of these two factors on maintenance of cocaine self-administration and reinstatement of cocaine seeking.

Methods: Male, Sprague-Dawley rats were trained to self-administer cocaine (0.2 mg/i.v. infusion; FR1) for 1 h per day for 10 sessions followed by short access (1 h/day), contingent long access (6 h/day), or noncontingent long access (1 h contingent + 5 h of yoked cocaine infusions/day; i.e., short access + yoked) to cocaine for 14 daily sessions. All rats underwent extinction training and were subsequently tested for the ability of cocaine-paired cues or a cocaine-priming injection (7.5 mg/kg i.p.) to reinstate extinguished cocaine seeking.

Results: Rats in all groups maintained stable responding for cocaine reinforcement and subsequently showed significant reinstatement of cocaine-seeking behavior. Conditioned-cued reinstatement was enhanced after the contingent long access and short access + yoked cocaine exposure relative to short access cocaine exposure. Conversely, cocaine-primed reinstatement was enhanced after contingent long-access cocaine exposure relative to the other two conditions.

Conclusions: Enhanced drug seeking produced by prolonged daily cocaine self-administration is due to a combination of behavioral and pharmacological factors. Specifically, conditioned-cued reinstatement is enhanced by increased cocaine intake and cocaine-primed reinstatement is enhanced by increased cocaine taking.

Publication types

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

MeSH terms

  • Animals
  • Cocaine / administration & dosage*
  • Conditioning, Psychological / drug effects
  • Cues
  • Exploratory Behavior / drug effects
  • Extinction, Psychological / drug effects*
  • Male
  • Motor Activity / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Reinforcement, Psychology
  • Self Administration*


  • Cocaine