Chronic Heart Failure Attenuates Oxytocin Signaling in the Central Amygdala

Heart failure (HF) is often accompanied by cognitive and mood disturbances, yet the underlying neurobiological mechanisms remain unclear. Oxytocin (OT) signaling in the hypothalamus–amygdala axis, particularly within the central amygdala (CeA), is known to regulate mood and anxiety-like behaviors. Using an ischemic rat model of HF, we investigated whether altered OTergic signaling contributes to mood dysfunction. We found that CeA OTergic innervation primarily originates from the supraoptic nucleus (SON). Although SON→CeA OT neuron numbers were unchanged, OT content and release at CeA terminals were reduced, accompanied by downregulation of neuronal and astrocytic OT receptors and impaired OT receptor–driven GABAergic transmission. These findings reveal that HF disrupts hypothalamus-to-amygdala OTergic circuitry, suggesting that targeting OT signaling or amygdalar GABAergic function may help mitigate mood impairments in HF.