Neuronal mechanisms of adenosine A2A receptors in the loss of consciousness induced by propofol general anesthesia with functional magnetic resonance imaging

Propofol is the most common intravenous anesthetic agent for induction and maintenance of anesthesia, and has been used clinically for more than 30 years. However, the mechanism by which propofol induces loss of consciousness (LOC) remains largely unknown. The adenosine A2A receptor (A2A R) has been extensively proven to have an effect on physiological sleep. It is, therefore, important to investigate the role of A2A R in the induction of LOC using propofol. In the present study, the administration of the highly selective A2A R agonist (CGS21680) and antagonist (SCH58261) was utilized to investigate the function of A2A R under general anesthesia induced by propofol by means of animal behavior studies, resting-state magnetic resonance imaging and c-Fos immunofluorescence staining approaches. Our results show that CGS21680 significantly prolonged the duration of LOC induced by propofol, increased the c-Fos expression in nucleus accumbens (NAc) and suppressed the functional connectivity of NAc-dorsal raphe nucleus (DR) and NAc-cingulate cortex (CG). However, SCH58261 significantly shortened the duration of LOC induced by propofol, decreased the c-Fos expression in NAc, increased the c-Fos expression in DR, and elevated the functional connectivity of NAc-DR and NAc-CG. Collectively, our findings demonstrate the important roles played by A2A R in the LOC induced by propofol and suggest that the neural circuit between NAc-DR maybe controlled by A2A R in the mechanism of anesthesia induced by propofol.