Reinforcer-dependent enhancement of operant responding in opioid-withdrawn rats

Ziva D. Cooper, Yong Gong Shi, James H. Woods

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Rationale and objective: Opioid withdrawal increases the reinforcing effectiveness of the μ-opioid agonist remifentanil in rodents. The current study explored the selectivity of this effect by assessing operant behavior maintained by drug and non-drug reinforcers, remifentanil, cocaine, a palatable liquid food, and standard food pellets, as a function of opioid dependence and withdrawal. Materials and methods: Operant responding exhibited by nondependent, morphine-naïve groups was compared with responding exhibited by morphine-dependent and withdrawn groups. Dependence was established using a noncontingent morphine dosing procedure that has been previously verified to maintain dependence while allowing for daily behavioral observation during a withdrawn state. Behavior maintained by remifentanil (0.10-10.0 μg/kg/infusion), cocaine (0.032-1.0 mg/kg/infusion), a palatable liquid food reinforcer (3.2-100.0% Vanilla Ensure® and water), or food pellets was assessed in dependent and nondependent groups. Results: Morphine withdrawal enhanced remifentanil self-administration, resulting in an upward and rightward shift of the descending limb of the dose-response curve, and increased operant responding for both food reinforcers. However, opioid withdrawal did not affect cocaine self-administration, nor did it affect responding for water. Conclusions: Enhanced operant responding observed under opioid-dependent and withdrawn conditions, while selective, is generalized to some nonopioid reinforcers.

Original languageEnglish (US)
Pages (from-to)369-378
Number of pages10
Issue number3
StatePublished - Oct 2010
Externally publishedYes


  • Cocaine
  • Dependence
  • Food
  • Morphine
  • Operant behavior
  • Opioid
  • Remifentanil
  • Self-administration

ASJC Scopus subject areas

  • Pharmacology


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