Nucleus accumbens and effort-related functions: behavioral and neural markers of the interactions between adenosine A2A and dopamine D2 receptors

Neuroscience. 2010 Apr 14;166(4):1056-67. doi: 10.1016/j.neuroscience.2009.12.056. Epub 2010 Jan 20.


Nucleus accumbens dopamine (DA) is a critical component of the brain circuitry regulating work output in reinforcement-seeking behavior and effort-related choice behavior. Moreover, there is evidence of an interaction between DA D(2) and adenosine A(2A) receptor function. Systemic administration of adenosine A(2A) antagonists reverses the effects of D(2) antagonists on tasks that assess effort related choice. The present experiments were conducted to determine if nucleus accumbens is a brain locus at which adenosine A(2A) and DA D(2) antagonists interact to regulate effort-related choice behavior. A concurrent fixed ratio 5 (FR5)/chow feeding procedure was used; with this procedure, rats can choose between completing an FR5 lever-pressing requirement for a preferred food (i.e., high carbohydrate operant pellets) or approaching and consuming a freely available food (i.e., standard rodent chow). Rats trained with this procedure spend most of their time pressing the lever for the preferred food, and eat very little of the concurrently available chow. Intracranial injections of the selective DA D(2) receptor antagonist eticlopride (1.0, 2.0, 4.0 microg) into nucleus accumbens core, but not a dorsal control site, suppressed FR5 lever-pressing and increased consumption of freely available chow. Either systemic or intra-accumbens injections of the adenosine A(2A) receptor antagonist MSX-3 reversed these effects of eticlopride on effort-related choice. Intra-accumbens injections of eticlopride also increased local expression of c-Fos immunoreactivity, and this effect was attenuated by co-administration of MSX-3. Adenosine and DA systems interact to regulate instrumental behavior and effort-related processes, and nucleus accumbens is an important locus for this interaction. These findings may have implications for the treatment of psychiatric symptoms such as psychomotor slowing, anergia and fatigue.

Publication types

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

MeSH terms

  • Adenosine / metabolism
  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology
  • Decision Making / drug effects
  • Decision Making / physiology
  • Dopamine / metabolism
  • Dopamine Antagonists / pharmacology
  • Feeding Behavior / drug effects
  • Feeding Behavior / physiology
  • Male
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism*
  • Proto-Oncogene Proteins c-fos / drug effects
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Adenosine A2A / drug effects*
  • Receptor, Adenosine A2A / metabolism*
  • Receptors, Dopamine D2 / drug effects*
  • Receptors, Dopamine D2 / metabolism*
  • Salicylamides / pharmacology
  • Xanthines / pharmacology


  • Dopamine Antagonists
  • MSX 3 compound
  • Proto-Oncogene Proteins c-fos
  • Receptor, Adenosine A2A
  • Receptors, Dopamine D2
  • Salicylamides
  • Xanthines
  • eticlopride
  • Adenosine
  • Dopamine