Role of dopamine D2-like receptors and their modulation by adenosine receptor stimulation in the reinstatement of methamphetamine seeking

  • Tracey A. Larson
  • Madeline C. Winkler
  • Jacob Stafford
  • Sophia C. Levis
  • Casey E. O’Neill
  • Ryan K. Bachtell
Original Investigation


Rationale and objective

Previous work has demonstrated that dopamine and adenosine receptors are involved in drug-seeking behaviors, yet the pharmacological interactions between these receptors in methamphetamine (MA) seeking are not well characterized. The present studies examined the role of the dopamine D2-like receptors in MA seeking and identified the interactive effects of adenosine receptor stimulation.


Adult male Sprague–Dawley rats were trained to lever press for MA in daily 2-h self-administration sessions on a fixed-ratio 1 schedule for 10 consecutive days. After 1 day of abstinence, lever pressing was extinguished in six daily extinction sessions. Treatments were administered systemically prior to a 2-h reinstatement test session.


An increase in MA seeking was observed following the administration of the dopamine D2-like agonist, quinpirole, or the D3 receptor agonist, 7-OH-DPAT. Stimulation of D2 or D4 receptors was ineffective at inducing MA seeking. Quinpirole-induced MA seeking was inhibited by D3 receptor antagonism (SB-77011A or PG01037), an adenosine A1 agonist, CPA, and an adenosine A2A agonist, CGS 21680. MA seeking induced by a MA priming injection or D3 receptor stimulation was inhibited by a pretreatment with the adenosine A1 agonist, CPA, but not the adenosine A2A agonist, CGS 21680.


These results demonstrate the sufficiency of dopamine D3 receptors to reinstate MA seeking that is inhibited when combined with adenosine A1 receptor stimulation.


Relapse Psychostimulant Purine Adenosine receptor Dopamine receptor 



This work was funded by National Institutes of Health (grant no. DA033358).

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.


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© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Psychology and Neuroscience and Center for NeuroscienceUniversity of Colorado BoulderBoulderUSA

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