Measuring mania-like elevated mood through amphetamine-induced 50-kHz ultrasonic vocalizations in rats

Br J Pharmacol. 2022 Sep;179(17):4201-4219. doi: 10.1111/bph.15487. Epub 2021 May 21.


Rats emit 50-kHz ultrasonic vocalizations (USV) in appetitive situations, reflecting a positive affective state. Particularly high rates of 50-kHz USV are elicited by the psychostimulant d-amphetamine. Exaggerated 50-kHz USV emission evoked by d-amphetamine is modulated by dopamine, noradrenaline and 5-hydroxytyrptamine receptor ligands and inhibited by the mood stabilizer lithium, the gold standard anti-manic drug for treating bipolar disorder. This indicates that exaggerated 50-kHz USV emission can serve as a reliable and valid measure for assessing mania-like elevated mood in rats with sufficient translational power for gaining a better understanding of relevant pathophysiological mechanisms and the identification of new therapeutic targets. The improved capacity to study the effects of anti-manic pharmacological interventions on a broader range of behaviours by including exaggerated 50-kHz USV emission as preclinical outcome measure complementary to locomotor hyperactivity will refine rodent models for mania. LINKED ARTICLES: This article is part of a themed issue on New discoveries and perspectives in mental and pain disorders. To view the other articles in this section visit

Keywords: amphetamine; bipolar disorder; dopamine; lithium; ultrasonic vocalizations.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine* / pharmacology
  • Animals
  • Antimanic Agents / pharmacology
  • Antimanic Agents / therapeutic use
  • Dextroamphetamine / pharmacology
  • Mania
  • Rats
  • Ultrasonics*
  • Vocalization, Animal


  • Antimanic Agents
  • Amphetamine
  • Dextroamphetamine