Effects of propofol on the dopamine, metabolites and GABAA receptors in media prefrontal cortex in freely moving rats

Recent researches indicate that the mechanism of anesthetic induce loss of consciousness (LOC) is related to dopamine dysfunction in the media prefrontal cortex (mPFC). Given GABAA receptors are the main target for commonly intravenous anesthetic propofol, in this study, we test whether that propofol induced LOC mediate by GABAA receptors in mPFC through altering the dopamine and its metabolites. In the present study, we use Loss of righting reflex (LORR) and Recovery of righting reflex (RORR) as measure to respectively reflect the status of unconsciousness and consciousness recovery in rats. We imitate the clinical anesthesia process, found the minimum of induction and maintenance concentration of propofol respectively was 11 mg/kg and 40 mg/kg per hour. Then, microdialysis technique was used to observe the change of dopamine (DA), metabolites 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) before and after intravenous infusion of propofol from caudal vein of freely moving rats. The results showed that propofol can increase the level of DOPAC except HVA, and reduced the level of DA in mPFC during unconsciousness of rats. DOPAC and DA return to the baseline level when the rats began to regain consciousness. Local reverse dialysis infusion of GABAA receptor antagonist GABAzine (50 uM) in mPFC can promote the time of LORR, reduce the time of RORR, and increase the basal level of DOPAC. With this condition, propofol increased HVA instead of DOPAC, whereas the DA was still reduced. These results suggest that propofol may induce unconsciousness by directly inhibiting dopamine release in the mPFC, and this effect does not be mediated by GABAA receptor in mPFC.