Positive emotional states have been shown to confer resilience to depression and anxiety in humans, but the molecular mechanisms underlying these effects have not yet been elucidated. In laboratory rats, positive emotional states can be measured by 50-kHz ultrasonic vocalizations (hedonic USVs), which are maximally elicited by juvenile rough-and-tumble play behavior. Using a focused microarray platform, insulin-like growth factor I (IGFI) extracellular signaling genes were found to be upregulated by hedonic rough-and-tumble play but not depressogenic social defeat. Administration of IGFI into the lateral ventricle increased rates of hedonic USVs in an IGFI receptor (IGFIR)-dependent manner. Lateral ventricle infusions of an siRNA specific to the IGFIR decreased rates of hedonic 50-kHz USVs. These results show that IGFI plays a functional role in the generation of positive affective states and that IGFI-dependent signaling is a potential therapeutic target for the treatment of depression and anxiety.
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