Modulation of ventral pallidal dopamine and glutamate release by the intravenous anesthetic propofol studied by in vivo microdialysis

The intravenous anesthetic propofol is reported to have various psychological side effects as hallucinations, sexual disinhibition, or euphoria. Hedonic and rewarding states like these are modulated by the dopaminergic system in the nucleus accumbens, prefrontal cortex and also in the ventral pallidum and by the glutamatergic system in the neocortex and limbic system. In the present study, propofol was administered either alone or in combination with the GABAA receptor antagonist bicuculline via reverse microdialysis into the ventral pallidum of freely moving rats. Dialysis fractions were taken every 20 min and analyzed for dopamine and glutamate using high performance liquid chromatography. Application of propofol decreased dopamine levels in the ventral pallidum. This effect seems to be mainly mediated through GABAA receptors, since it was compensated by the GABAA receptor antagonist bicuculline. Propofol and propofol plus bicuculline exerted no effect on glutamate release in this brain region. The reduced dopamine release in ventral pallidum was most probably mediated through a GABAergic feedback loop from the ventral pallidum via the nucleus accumbens to the dopaminergic neurons of the ventral tegmental area or by long loop feedback. As an increase but not a decrease of dopamine release in the ventral pallidum is involved in hedonic and rewarding properties, similar symptoms induced by propofol seem to be unrelated to an action of propofol in the ventral pallidum.