Adenosine A1 receptor in the medial parabrachial nucleus modulates sleep-wake regulation and homeostatic processes

To elucidate the role of adenosine A1 receptors (A1R) in the medial parabrachial nucleus (MPB) for bidirectional sleep-wake regulation and homeostatic control. Bilateral microinjections targeted the MPB in rats, administering: adenosine (0.5/1.5/4.5 nmol), A1R agonist CPA (1.5 nmol), A1R antagonist CPT (1.7 nmol), or adenosine deaminase inhibitor EHNA (2.0 nmol). Sleep architecture was quantified via EEG/EMG, with histological verification of MPB targeting. Adenosineergic modulation: 4.5 nmol adenosine increased NREM sleep by 149.1% (P = 0.0002) and reduced wakefulness by 47.6% (P = 0.0004). Endogenous amplification: EHNA elevated NREM sleep by 85.2% (P = 0.019), confirming physiological adenosine action. A1R-specificity: CPA mimicked adenosine (NREM ↑63.2%, P = 0.011), whereas CPT increased wakefulness by 46.3% (P = 0.021). Homeostasis disruption: Following sleep deprivation，CPT attenuated post-deprivation rebound (NREM recovery ↓43.8%, P = 0.042; REM rebound abolished). A1R in the MPB critically regulates NREM sleep and contributes to homeostatic responses through bidirectional adenosine signaling, identifying this brainstem nucleus as a novel regulatory hub. Dose-dependent efficacy (threshold: 1.5 nmol) suggests therapeutic potential for sleep disorders.