Adenosine A(2A) receptor antagonism reverses the effects of dopamine receptor antagonism on instrumental output and effort-related choice in the rat: implications for studies of psychomotor slowing

Psychopharmacology (Berl). 2007 Apr;191(3):579-86. doi: 10.1007/s00213-006-0554-5. Epub 2006 Oct 27.


Rationale: Organisms frequently make effort-related decisions based upon assessments of motivational value and response costs. Energy-related dysfunctions such as psychomotor slowing and apathy are critically involved in some clinical syndromes. Dopamine (DA), particularly in the nucleus accumbens, regulates effort-related processes. Dopamine antagonism and accumbens dopamine depletions cause rats performing on choice tasks to reallocate their behavior away from food-reinforced tasks that have high response requirements.

Objective: There is evidence of a functional interaction between DA and adenosine A(2A) receptors in the neostriatum and nucleus accumbens. The present experiments were conducted to determine if adenosine A(2A) receptor antagonism could reverse the effects of dopamine receptor antagonism on instrumental behavior and effort-related choice.

Materials and methods: The adenosine A(2A) receptor antagonist MSX-3 was investigated for its ability to reverse the effects of the dopamine receptor antagonist haloperidol (0.1 mg/kg) on fixed ratio 5 instrumental lever-pressing and on response allocation using a concurrent lever-pressing/chow-feeding choice task.

Results: Haloperidol significantly suppressed fixed ratio 5 responding, and with rats responding on the concurrent choice task, it altered choice behavior, significantly reducing lever-pressing for food and increasing chow intake. Injections of MSX-3 (0.5-2.0 mg/kg) produced a dose-related attenuation of the effects of 0.1 mg/kg haloperidol on both tasks. The high dose of MSX-3, when administered in the absence of haloperidol, did not significantly affect responding on either task.

Conclusions: Adenosine and dopamine systems interact to regulate instrumental behavior and effort-related processes, which may have implications for the treatment of psychiatric symptoms such as psychomotor slowing or anergia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine A2 Receptor Antagonists*
  • Animals
  • Behavior, Animal / drug effects*
  • Brain / drug effects*
  • Brain / metabolism
  • Choice Behavior / drug effects*
  • Conditioning, Operant / drug effects*
  • Dopamine Antagonists / pharmacology*
  • Dose-Response Relationship, Drug
  • Haloperidol / pharmacology
  • Male
  • Motivation
  • Motor Activity / drug effects
  • Neostriatum / drug effects
  • Nucleus Accumbens / drug effects
  • Physical Exertion
  • Psychomotor Performance / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adenosine A2 / metabolism
  • Receptors, Dopamine / drug effects*
  • Receptors, Dopamine / metabolism
  • Reinforcement Schedule
  • Xanthines / pharmacology*


  • Adenosine A2 Receptor Antagonists
  • Dopamine Antagonists
  • MSX 3 compound
  • Receptors, Adenosine A2
  • Receptors, Dopamine
  • Xanthines
  • Haloperidol