Effects of sex and remifentanil dose on rats' acquisition of responding for a remifentanil-conditioned reinforcer

Jeremiah W. Bertz, Emily L. Jackson, Davina R. Barron, James H. Woods

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Opioid-conditioned reinforcement is thought to exacerbate opioid abuse and dependence. Sex/gender can influence opioid abuse behaviors, but the effects of sex/gender on opioid-conditioned reinforcement, specifically, are unclear. In this study, we compared new-response acquisition with opioid-conditioned reinforcement in male and female rats. First, separate groups received response-independent remifentanil injections (0.0-32.0 μg/kg, intravenous) and presentations of a light-noise stimulus. In the experimental groups, injections and stimulus presentations always cooccurred [paired Pavlovian conditioning (PAV)]; in the control groups, the two occurred independently of each other (random PAV). Next, in the instrumental acquisition (ACQ) sessions, two novel nose-poke manipulanda were introduced. All animals (regardless of sex, dose, and PAV type) could respond in the active nose-poke, which produced the stimulus alone, or in the inactive nose-poke. Both males and females dose-dependently acquired nosepoke responding (active>inactive) after paired PAV, but not after random PAV. Therefore, the stimulus was a conditioned reinforcer. We identified three sex differences. First, only females acquired responding after paired PAV with 32.0 μg/kg remifentanil. Second, using a progressive ratio schedule for ACQ, both sexes acquired responding, but females made significantly more active responses. Third, when a single session of PAV was conducted, only males acquired responding. Thus, rats' sex interacts with pharmacological and environmental factors to determine opioid-conditioned reinforcement.

Original languageEnglish (US)
Pages (from-to)137-147
Number of pages11
JournalBehavioural pharmacology
Issue number2-3
StatePublished - Apr 2016
Externally publishedYes


  • Conditioned reinforcement
  • Cues
  • Drug abuse
  • New-response acquisition
  • Opioid
  • Pavlovian conditioning
  • Rat
  • Sex difference

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health


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