Endocannabinoid signaling in the stress response of male and female songbirds.

Endocannabinoid (eCB) signaling plays an important role in the stress response pathways of the mammalian brain, yet its role in the avian stress response has not been described. Understanding eCB signaling in avian species (such as the European starling, Sturnus vulgaris) allows a model system that exhibits natural attenuation of hypothalamic-pituitary-adrenal (HPA) responsiveness to stressors. Specifically, seasonally-breeding birds exhibit highest HPA activity during the breeding season and subsequently exhibit robust HPA down-regulation during molt. As eCB signaling in mammals has an overall inhibitory effect on HPA activity, we expected shifts in eCB signaling to regulate the seasonal HPA down-regulation during molt. However, our data did not support a role for eCB signaling in molt-related suppression of HPA activity. For example, injection of the cannabinoid receptor (CB1) antagonist, AM251 did not potentiate molt-suppressed HPA activity. Instead, our data suggest eCB regulation of HPA plasticity as birds transition from breeding to molt. In support of this hypothesis, birds in late breeding season demonstrated a more dynamic response at the level of avian amygdala eCB content in response to acute stress. The response and directionality of this effect match that seen in mammals. Overall, our data suggest eCB signaling may allow for dynamic range in HPA responsiveness (e.g., breeding) but the signaling pathway’s role may be limited when the HPA response is restrained (e.g., molt). This first characterization of eCB signaling in the avian stress response also emphasizes that while the system functions similarly to other species, its exact role may be species-specific.