Selection of sucrose concentration depends on the effort required to obtain it: studies using tetrabenazine, D1, D2, and D3 receptor antagonists

Psychopharmacology (Berl). 2015 Jul;232(13):2377-91. doi: 10.1007/s00213-015-3872-7. Epub 2015 Feb 3.


Rationale: Low doses of dopamine (DA) antagonists and accumbens DA depletions reduce food-reinforced instrumental behavior but do not impair primary food motivation, causing animals to reallocate behavior away from food-reinforced tasks with high response requirements and select less effortful alternatives. However, it is uncertain if this same pattern of effects would occur if sucrose was used as the reinforcer.

Objectives: These experiments studied the impact of DA depletion and antagonism on performance of an effort-related choice task using sucrose as the reinforcer, as well as sucrose consumption, preference, and taste reactivity tests.

Methods: The effects of DA manipulations were assessed using a task in which rats chose between lever pressing on a fixed ratio 7 schedule for 5.0 % sucrose versus freely consuming a less concentrated solution (0.3 %).

Results: The DA depleting agent tetrabenazine shifted effort-related choice, decreasing lever pressing for 5.0 % sucrose but increasing intake of the concurrently available 0.3 % sucrose. Tetrabenazine did not affect sucrose appetitive taste reactivity, or sucrose consumption or preference, in free consumption tests. The D1 antagonist ecopipam and the D2 antagonist haloperidol also shifted choice behavior at doses that did not alter sucrose consumption or preference. In contrast, sucrose pre-exposure reduced consumption across all conditions. D3 antagonism had no effects.

Conclusions: D1 and D2 receptor blockade and DA depletion reduce the tendency to work for sucrose under conditions that leave fundamental aspects of sucrose motivation (intake, preference, hedonic reactivity) intact. These findings have implications for studies employing sucrose intake or preference in animal models of depression.

Keywords: Anergia; Anhedonia; Decision making; Depression; Dopamine; Motivation.

Publication types

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

MeSH terms

  • Animals
  • Choice Behavior / drug effects
  • Choice Behavior / physiology
  • Dopamine Antagonists / pharmacology*
  • Dopamine D2 Receptor Antagonists / pharmacology
  • Dose-Response Relationship, Drug
  • Male
  • Motivation / drug effects
  • Motivation / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / antagonists & inhibitors
  • Receptors, Dopamine D1 / physiology*
  • Receptors, Dopamine D2 / physiology*
  • Receptors, Dopamine D3 / antagonists & inhibitors
  • Receptors, Dopamine D3 / physiology*
  • Sucrose / administration & dosage*
  • Tetrabenazine / pharmacology*


  • Dopamine Antagonists
  • Dopamine D2 Receptor Antagonists
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Sucrose
  • Tetrabenazine