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 A(2A)receptor (A(2A)R) has been extensively proven to have an effect on physiological sleep. It is, therefore, important to investigate the role of A(2A)R in the induction of LOC using propofol. In the present study, the administration of the highly selective A(2A)R agonist (CGS21680) and antagonist (SCH58261) was utilized to investigate the function of A(2A)R under general anesthesia induced by propofol by means of animal behavior studies, resting-state magnetic resonance imaging andc-Fos immunofluorescence staining approaches. Our results show that CGS21680 significantly prolonged the duration of LOC induced by propofol, increased thec-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 thec-Fos expression in NAc, increased thec-Fos expression in DR, and elevated the functional connectivity of NAc-DR and NAc-CG. Collectively, our findings demonstrate the important roles played by A(2A)R in the LOC induced by propofol and suggest that the neural circuit between NAc-DR maybe controlled by A(2A)R in the mechanism of anesthesia induced by propofol.

Automated summary

The study demonstrates the important roles played by A(2A) receptor in the loss of consciousness induced by propofol, suggesting that the neural circuit between NAc-DR may be controlled by A(2A)R in the mechanism of anesthesia induced by propofol.