Dexmedetomidine Inhibits Paraventricular Corticotropin-releasing Hormone Neurons that Attenuate Acute Stress-induced Anxiety-like Behavior in Mice

Background Dexmedetomidine has repeatedly shown to improve anxiety, but the precise neural mechanisms underlying this effect remain incompletely understood. This study aims to explore the role of corticotropin-releasing hormone–producing hypothalamic paraventricular nucleus (CRH PVN ) neurons in mediating the anxiolytic effects of dexmedetomidine. Methods A social defeat stress mouse model was used to evaluate the anxiolytic effects induced by dexmedetomidine through the elevated plus maze, open-field test, and measurement of serum stress hormone levels. In vivo Ca 2+ signal fiber photometry and ex vivo patch-clamp recordings were used to determine the excitability of CRH PVN neurons and investigate the specific mechanism involved. CRH PVN neuron modulation was achieved through chemogenetic activation or inhibition. Results Compared with saline, dexmedetomidine (40 µg/kg) alleviated anxiety-like behaviors. Additionally, dexmedetomidine reduced CRH PVN neuronal excitability. Chemogenetic activation of CRH PVN neurons decreased the time spent in the open arms of the elevated plus maze and in the central area of the open-field test. Conversely, chemogenetic inhibition of CRH PVN neurons had the opposite effect. Moreover, the suppressive impact of dexmedetomidine on CRH PVN neurons was attenuated by the α 2 -receptor antagonist yohimbine. Conclusions The results indicate that the anxiety-like effects of dexmedetomidine are mediated via α 2 -adrenergic receptor–triggered inhibition of CRH PVN neuronal excitability in the hypothalamus. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New