Hypothalamic oxytocin neurons drive pro-anxiety effects via glutamatergic projections to the lateral hypothalamus

Anxiety disorders are a significant public health concern, often involving complex neural circuits. While oxytocin is widely recognized for its prosocial and anxiolytic roles, its precise involvement in fear and anxiety responses is nuanced and context-dependent. The lateral hypothalamus (LH), a key brain region, integrates diverse signals to regulate arousal, stress, and motivated behaviors. Understanding specific oxytocin pathways that might promote anxiety, rather than alleviate it, is crucial for developing targeted therapeutic strategies and refining our understanding of this versatile neuropeptide's actions. This study investigates such a pathway.

Researchers investigated the role of hypothalamic oxytocin neurons in anxiety using a preclinical model. Female subjects were subjected to six weeks of isolation, a known stressor, and subsequently assessed for anxiety-like behaviors using an elevated plus maze. The study examined changes in oxytocin receptor (OXTR) expression in the nucleus accumbens (NAc) and the activation of paraventricular nucleus (PVN) oxytocin neurons projecting to the NAc. Functional connectivity and neurotransmitter systems were explored for hypothalamic oxytocin neuron projections to the lateral hypothalamus (LH), focusing on glutamatergic signaling.