Effects of adenosine A2A receptor stimulation on cocaine-seeking behavior in rats

Ryan K. Bachtell, David W. Self

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Rationale: Dopamine (DA) receptor stimulation in the nucleus accumbens (NAc) plays an important role in regulating cocaine-seeking behavior. Adenosine receptors antagonize the effects of DA receptor stimulation on intracellular signaling, neuronal output, and behavior. Objectives: The goal of the present study is to determine the effects of adenosine A2A receptor stimulation on reinstatement of cocaine-seeking behavior in rats. Methods: Rats were trained to lever press for cocaine in daily self-administration sessions on a fixed-ratio 1 schedule for 3 weeks. After 1 week of abstinence, lever pressing was extinguished in six daily extinction sessions. We subsequently assessed the effects of the adenosine A2A receptor agonist, CGS 21680, on cocaine-, quinpirole (D2 agonist)-, and cue-induced reinstatement to cocaine seeking. We also assessed the effects of CGS 21680 on sucrose seeking in rats extinguished from sucrose self-administration. Results: Pretreatment of CGS 21680 dose-dependently blunted cocaine-induced reinstatement (15 mg/kg, i.p.). Pretreatment with CGS 21680 (0.03 mg/kg, i.p.) also attenuated quinpirole- and cue-induced reinstatement. A minimally effective dose of CGS 21680 failed to alter cocaine-induced locomotor activity or sucrose seeking. Conclusions: Stimulation of adenosine A2A receptors antagonizes reinstatement of cocaine seeking elicited by cocaine, DA D 2-receptor stimulation, and cocaine-conditioned cues. These findings suggest that adenosine A2A receptor stimulation may oppose DA D 2 receptor signaling in the NAc that mediates cocaine relapse.

Original languageEnglish (US)
Pages (from-to)469-478
Number of pages10
Issue number3
StatePublished - 2009


  • A receptor
  • Craving
  • D receptor
  • Incentive motivation
  • Reinstatement
  • Relapse
  • Reward
  • Self-administration

ASJC Scopus subject areas

  • Pharmacology


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