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 (AMPH). Exaggerated 50-kHz USV emission evoked by AMPH is modulated by dopamine, noradrenaline, and serotonin 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 behaviors by including exaggerated 50-kHz USV emission as preclinical outcome measure complementary to locomotor hyperactivity will refine rodent models for mania.
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