Drinking sucrose or saccharin enhances sensitivity of rats to quinpirole-induced yawning

Eur J Pharmacol. 2015 Oct 5:764:529-536. doi: 10.1016/j.ejphar.2015.07.036. Epub 2015 Jul 17.


Diet can impact sensitivity of rats to some of the behavioral effects of drugs acting on dopamine systems. The current study tested whether continuous access to sucrose is necessary to increase yawning induced by the dopamine receptor agonist quinpirole, or if intermittent access is sufficient. These studies also tested whether sensitivity to quinpirole-induced yawning increases in rats drinking the non-caloric sweetener saccharin. Dose-response curves (0.0032-0.32 mg/kg) for quinpirole-induced yawning were determined once weekly in rats with free access to standard chow and either continuous access to water, 10% sucrose solution, or 0.1% saccharin solution, or intermittent access to sucrose or saccharin (i.e., 2 days per week with access to water on other days). Cumulative doses of quinpirole increased then decreased yawning, resulting in an inverted U-shaped dose-response curve. Continuous or intermittent access to sucrose enhanced sensitivity to quinpirole-induced yawning. Continuous, but not intermittent, access to saccharin also enhanced sensitivity to quinpirole-induced yawning. In all groups, pretreatment with the selective D3 receptor antagonist PG01037 shifted the ascending limb of the quinpirole dose-response curve to the right, while pretreatment with the selective D2 receptor antagonist L-741,626 shifted the descending limb to the right. These results suggest that even intermittent consumption of diets containing highly palatable substances (e.g. sucrose) alters sensitivity to drugs acting on dopamine systems in a manner that could be important in vulnerability to abuse drugs.

Keywords: Dopamine receptor; Fat; Intermittent access; Quinpirole; Rat; Saccharin; Sucrose; Yawning.

Publication types

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

MeSH terms

  • Administration, Oral
  • Animals
  • Behavior, Animal / drug effects*
  • Benzamides / pharmacology*
  • Dietary Sucrose / administration & dosage*
  • Dopamine D2 Receptor Antagonists / pharmacology
  • Dose-Response Relationship, Drug
  • Drinking*
  • Drug Administration Schedule
  • Drug Interactions
  • Indoles / pharmacology
  • Male
  • Non-Nutritive Sweeteners / administration & dosage*
  • Piperidines / pharmacology
  • Pyridines / pharmacology*
  • Quinpirole / pharmacology*
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D3 / antagonists & inhibitors
  • Receptors, Dopamine D3 / metabolism
  • Saccharin / administration & dosage*
  • Yawning / drug effects*


  • Benzamides
  • Dietary Sucrose
  • Dopamine D2 Receptor Antagonists
  • Indoles
  • N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)but-2-enyl)-4-pyridine-2-ylbenzamide
  • Non-Nutritive Sweeteners
  • Piperidines
  • Pyridines
  • Receptors, Dopamine D3
  • Quinpirole
  • 3-(4-(4-chlorophenyl-4-hydroxypiperidino)methyl)indole
  • Saccharin