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

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.

High-frequency ultrasonic vocalizations in rats in response to tickling: the effects of restraint stress.

We tested the hypotheses that (a) the propensity to emit high-frequency (∼50 kHz) ultrasonic vocalizations in response to manual "tickling" by an experimenter, may serve as a behavioral marker of positive affect in rats and, (b) that tickling may reduce the severity of stress. Group-housed adult rats were subjected to the 15-s tickling procedure daily, and their ultrasonic vocalization response was measured over a period of two weeks, until it has stabilized. The animals were then subjected to the restraint stress lasting for one week. The experimental groups were exposed to stress 1 h before or 1 h after tickling and the controls were tickled without stressing. Rats that were stressed 1 h before tickling demonstrated a decreased number of the high-frequency calls as compared with the non-stressed controls. Stressing 23 h before tickling reduced the call response less effectively. The propensity to emit high-frequency calls has normalized 7 and 12 days following the end of stressing. In addition, stressed groups showed a diminution of sucrose preference, which in the case of rats stressed 23 h before tickling persisted even for 12 days following the end of restraint. The present data suggest that repeated stress may decrease the propensity to produce high-frequency vocalizations, and that this measure may serve as a biomarker of the depressive state of animals.

Laughing rats are optimistic.

Emotions can bias human decisions- for example depressed or anxious people tend to make pessimistic judgements while those in positive affective states are often more optimistic. Several studies have reported that affect contingent judgement biases can also be produced in animals. The animals, however, cannot self-report; therefore, the valence of their emotions, to date, could only be assumed. Here we present the results of an experiment where the affect-contingent judgement bias has been produced by objectively measured positive emotions. We trained rats in operant Skinner boxes to press one lever in response to one tone to receive a food reward and to press another lever in response to a different tone to avoid punishment by electric foot shock. After attaining a stable level of discrimination performance, the animals were subjected to either handling or playful, experimenter-administered manual stimulation - tickling. This procedure has been confirmed to induce a positive affective state in rats, and the 50-kHz ultrasonic vocalisations (rat laughter) emitted by animals in response to tickling have been postulated to index positive emotions akin to human joy. During the tickling and handling sessions, the numbers of emitted high-frequency 50-kHz calls were scored. Immediately after tickling or handling, the animals were tested for their responses to a tone of intermediate frequency, and the pattern of their responses to this ambiguous cue was taken as an indicator of the animals' optimism. Our findings indicate that tickling induced positive emotions which are directly indexed in rats by laughter, can make animals more optimistic. We demonstrate for the first time a link between the directly measured positive affective state and decision making under uncertainty in an animal model. We also introduce innovative tandem-approach for studying emotional-cognitive interplay in animals, which may be of great value for understanding the emotional-cognitive changes associated with mood disorders.