Ultrasound vocalization is not related to corticosterone response in isolated rat pups

Isolated from their mother, rat pups respond with changes in ultrasound vocalization (USV), a paradigm that can be used as a test for a large range of anxiolytics. Because the relation between corticosterone (CORT) and putative stress responses like USV is not clear, we examined the effects of the benzodiazepine drugs chlordiazepoxide and diazepam vs. the nonbenzodiazepine drugs buspirone and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on USV and plasma CORT concentrations. All drugs caused a dose-related decrease in USV, but only buspirone and 8-OH-DPAT induced a dose-related increase in CORT. We suggest that the seemingly paradoxical effects of buspirone and 8-OH-DPAT, that is, the decrease in USV and the concomitant increase in plasma CORT, are due to the fact that these two drugs act as full agonists at both pre- and postsynaptic 5-HT1A receptors. Our results indicate that, when measured as an increase in the activity of the pituitary adrenocortical axis, the stress response can be interpreted in markedly different ways, depending on whether the increased activity is elicited by an environmental stressor or by pharmacological manipulation.