Halothane enhances dopamine metabolism at presynaptic sites in a calcium-independent manner in rat striatum

Background. We have previously reported that halothane anaesthesiaincreases the extracellular concentration of dopamine (DA) metabolitesin the rat striatum with no change in DA. Although the metabolismof catecholamines is a source of oxidative stress, there islittle information about DA metabolism and anaesthesia. We assessedthe mechanism(s) of enhanced DA metabolism induced by halothane. Methods. Microdialysis probes were implanted into male Sprague–Dawleyrats and perfused with artificial cerebrospinal fluid (CSF).The dialysate was injected directly into an HPLC every 20 min.Each group of rats (n=5–7) was administered saline, apomorphine100 µg kg^–1, pargyline 7.5 or 75 mg kg^–1,reserpine 2 mg kg^–1 or -methyl-p-tyrosine (AMPT) 250 mgkg^–1. Another set of rats was perfused with artificialCSF containing tetrodotoxin (TTX) 1 µM or calcium-freeCSF containing 10 mM EGTA. Rats were anaesthetized with halothane0.5 or 1.5% 1 h after pharmacological treatments. Results. In rats pretreated with apomorphine, despite a decreasein DA concentration, halothane induced a increase in DA metabolites.Pargyline (high dose) and reserpine completely and AMPT partiallyantagonized the increase in DA metabolites induced by halothaneanaesthesia. TTX perfusion reduced the increase in DA, whereascalcium-free CSF perfusion did not. Conclusions. Our data suggest that halothane accelerates DAmetabolism at presynaptic sites by releasing DA from reserpine-sensitivestorage vesicles to the cytoplasm in a calcium-independent manner.The metabolic oxidative stress of inhalation anaesthesia requiresfuture investigation.