Dopaminergic modulation of effort-related choice behavior as assessed by a progressive ratio chow feeding choice task: pharmacological studies and the role of individual differences

PLoS One. 2012;7(10):e47934. doi: 10.1371/journal.pone.0047934. Epub 2012 Oct 22.


Mesolimbic dopamine (DA) is involved in behavioral activation and effort-related processes. Rats with impaired DA transmission reallocate their instrumental behavior away from food-reinforced tasks with high response requirements, and instead select less effortful food-seeking behaviors. In the present study, the effects of several drug treatments were assessed using a progressive ratio (PROG)/chow feeding concurrent choice task. With this task, rats can lever press on a PROG schedule reinforced by a preferred high-carbohydrate food pellet, or alternatively approach and consume the less-preferred but concurrently available laboratory chow. Rats pass through each ratio level 15 times, after which the ratio requirement is incremented by one additional response. The DA D(2) antagonist haloperidol (0.025-0.1 mg/kg) reduced number of lever presses and highest ratio achieved but did not reduce chow intake. In contrast, the adenosine A(2A) antagonist MSX-3 increased lever presses and highest ratio achieved, but decreased chow consumption. The cannabinoid CB1 inverse agonist and putative appetite suppressant AM251 decreased lever presses, highest ratio achieved, and chow intake; this effect was similar to that produced by pre-feeding. Furthermore, DA-related signal transduction activity (pDARPP-32(Thr34) expression) was greater in nucleus accumbens core of high responders (rats with high lever pressing output) compared to low responders. Thus, the effects of DA antagonism differed greatly from those produced by pre-feeding or reduced CB1 transmission, and it appears unlikely that haloperidol reduces PROG responding because of a general reduction in primary food motivation or the unconditioned reinforcing properties of food. Furthermore, accumbens core signal transduction activity is related to individual differences in work output.

Publication types

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

MeSH terms

  • 3,3'-Diaminobenzidine
  • Adenosine A2 Receptor Antagonists / pharmacology
  • Analysis of Variance
  • Animal Feed / analysis
  • Animal Nutritional Physiological Phenomena / physiology*
  • Animals
  • Choice Behavior / physiology*
  • Dopamine / metabolism*
  • Dopamine Antagonists / pharmacology
  • Dopamine and cAMP-Regulated Phosphoprotein 32 / metabolism
  • Feeding Behavior / drug effects*
  • Haloperidol / pharmacology
  • Immunohistochemistry
  • Individuality*
  • Male
  • Piperidines
  • Pyrazoles
  • Rats
  • Rats, Sprague-Dawley
  • Xanthines / pharmacology


  • Adenosine A2 Receptor Antagonists
  • Dopamine Antagonists
  • Dopamine and cAMP-Regulated Phosphoprotein 32
  • MSX 3 compound
  • Piperidines
  • Ppp1r1b protein, rat
  • Pyrazoles
  • Xanthines
  • 3,3'-Diaminobenzidine
  • AM 251
  • Haloperidol
  • Dopamine