Intra-accumbens injections of the adenosine A2A agonist CGS 21680 affect effort-related choice behavior in rats

Psychopharmacology (Berl). 2008 Sep;199(4):515-26. doi: 10.1007/s00213-008-1174-z. Epub 2008 May 20.


Rationale: Nucleus accumbens dopamine (DA) participates in the modulation of instrumental behavior, including aspects of behavioral activation and effort-related choice behavior. Rats with impaired accumbens DA transmission reallocate their behavior away from food-reinforced activities that have high response requirements and instead select less-effortful types of food-seeking behavior. Although accumbens DA is considered a critical component of the brain circuitry regulating effort-related processes, emerging evidence also implicates adenosine A(2A) receptors.

Objective: The present work was undertaken to test the hypothesis that accumbens A(2A) receptor stimulation would produce effects similar to those produced by DA depletion or antagonism.

Materials and methods: Three experiments assessed the effects of the adenosine A(2A) agonist CGS 21680 on performance of a concurrent choice task (lever pressing for preferred food vs. intake of less preferred chow) that is known to be sensitive to DA antagonists and accumbens DA depletions.

Results: Systemic injections of CGS 21680 reduced lever pressing but did not increase feeding. In contrast, bilateral infusions of the adenosine A(2A) receptor agonist CGS 21680 (6.0-24.0 ng) into the nucleus accumbens decreased lever pressing for the preferred food but substantially increased consumption of the less preferred chow. Injections of CGS 21680 into a control site dorsal to the accumbens were ineffective.

Conclusions: Taken together, these results are consistent with the hypothesis that local stimulation of adenosine A(2A) receptors in nucleus accumbens produces behavioral effects similar to those induced by accumbens DA depletions. Accumbens adenosine A(2A) receptors appear to be a component of the brain circuitry regulating effort-related choice behavior.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / administration & dosage
  • Adenosine / analogs & derivatives*
  • Adenosine / pharmacology
  • Adenosine A2 Receptor Agonists*
  • Animals
  • Choice Behavior / drug effects*
  • Conditioning, Operant / drug effects
  • Data Interpretation, Statistical
  • Dose-Response Relationship, Drug
  • Injections, Intraperitoneal
  • Male
  • Microinjections
  • Nucleus Accumbens / physiology*
  • Phenethylamines / administration & dosage
  • Phenethylamines / pharmacology*
  • Physical Exertion / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Reinforcement Schedule


  • Adenosine A2 Receptor Agonists
  • Phenethylamines
  • 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
  • Adenosine