Citrulline stimulates locomotor activity in aged rats: Implication of the dopaminergic pathway

Nutrition. 2017 Jun;38:9-12. doi: 10.1016/j.nut.2017.01.001. Epub 2017 Jan 9.


Objectives: A citrulline (CIT)-enriched diet improves locomotor activity in aged rats, but the underlying mechanism is unknown. The aim of this study was to determine the effect of CIT administration on locomotor activity and dopamine activity in healthy aged rats.

Methods: Sixty adult (3-mo-old) and aged (20-mo-old) rats were divided into four groups (n = 15 each) stratified by age (adult versus old) and diet (control versus CIT; i.e., Ad-Control, Ad-CIT, Old-Control, Old-CIT) and fed for 4 d on either a CIT-enriched diet (5 g/kg daily; Ad-CIT and Old-CIT) or an isonitrogeneous control diet (Ad-Control and Old-Control). Locomotor activity was evaluated in a Y-maze. On day 5, animals were sacrificed and brain (striatum) was removed to determine total and phosphorylated forms of tyrosine hydroxylase (TH) by immunohistochemistry.

Results: CIT restored locomotor activity in aged rats (arm visits: Old-CIT 28 ± 1 versus Old-Control 23 ± 1; P < 0.05), associated with an increase in total TH (Old-CIT 668 ± 27 versus Old-Control 529 ± 22; P < 0.05) and phosphorylated forms of TH (Old-CIT 1012 ± 39 versus Old-Control 589 ± 69; P < 0.05).

Conclusion: In aged rats, CIT is able to stimulate locomotor activity via the dopaminergic pathway.

Keywords: Aging; Amino acids; Locomotor activity; Tyrosine hydroxylase.

MeSH terms

  • Age Factors
  • Animals
  • Behavior, Animal / drug effects*
  • Citrulline / pharmacology*
  • Dopamine / metabolism*
  • Locomotion / drug effects*
  • Models, Animal
  • Rats
  • Rats, Sprague-Dawley


  • Citrulline
  • Dopamine