Inhibition of the glucocorticoid synthesis reverses stress-induced decrease in rat's 50-kHz ultrasonic vocalizations

• Manual somatosensory stimulation (“tickling”) results in a positive affect in rats.
• The positive affect triggers emission of 50-kHz ultrasonic vocalizations (USVs).
• Prolonged restraint stress diminished “tickling”-induced 50-kHz USVs.
• Metyrapone inhibits the synthesis of glucocorticoids.
• Metyrapone prevented stress-induced decrease in expression of positive affect.

The playful, experimenter-administered manual somatosensory stimulation of rats results in a positive affect that triggers emission of ∼50-kHz ultrasonic vocalizations (USVs), which have been proposed to index positive emotions akin to human joy and laughter. Our earlier findings showed that restraint stress decreased rat's tendency to emit 50-kHz USVs. Here we investigated whether the effects of stress on “tickling”-induced vocalizations could be alleviated by the glucocorticoid synthesis inhibitor, metyrapone. After the daily tickling sessions carried out until the USV response to tickling has stabilized, the rats were subjected to either handling, handling and metyrapone treatment, restraint stress lasting one week or the restraint stress and metyrapone treatment. Our results confirmed that animals exposed to restraint stress diminish the number of “tickling”-induced vocalizations as compared to the “tickled” but handled conspecifics. Metyrapone treatment prevented this effect in stressed animals having no effects in handled rats. The off-line analysis revealed that the majority (82–88%) of “tickling”-induced USVs were of the 50-kHz frequency modulated type and that the flat USVs appeared much less frequently (8.5–12%) while the 22-kHz alarm calls appeared sporadically (0.3–8%). Moreover, the acoustic parameters of the 50-kHz frequency modulated and flat USVs resembled the calls described earlier in adult rats. The results of the present study offer a way of identifying anti-stress and perhaps anti-depressant action of novel compounds based on the measurement of a positive affect of animals.