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

Abstract

Background. We have previously reported that halothane anaesthesia increases the extracellular concentration of dopamine (DA) metabolites in the rat striatum with no change in DA. Although the metabolism of catecholamines is a source of oxidative stress, there is little information about DA metabolism and anaesthesia. We assessed the mechanism(s) of enhanced DA metabolism induced by halothane. Methods. Microdialysis probes were implanted into male Sprague-Dawley rats 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, apomorphine 100 μg kg=1, pargyline 7.5 or 75 mg kg-1, reserpine 2 mg kg-1 or α-methyl-p-tyrosine (AMPT) 250 mg kg-1. Another set of rats was perfused with artificial CSF containing tetrodotoxin (TTX) 1 μM or calcium-free CSF containing 10 mM EGTA. Rats were anaesthetized with halothane 0.5 or 1.5% 1 h after pharmacological treatments. Results. In rats pretreated with apomorphine, despite a decrease in DA concentration, halothane induced a increase in DA metabolites. Pargyline (high dose) and reserpine completely and AMPT partially antagonized the increase in DA metabolites induced by halothane anaesthesia. TTX perfusion reduced the increase in DA, whereas calcium-free CSF perfusion did not. Conclusions. Our data suggest that halothane accelerates DA metabolism at presynaptic sites by releasing DA from reserpine-sensitive storage vesicles to the cytoplasm in a calcium-independent manner. The metabolic oxidative stress of inhalation anaesthesia requires future investigation. © The Board of Management and Trustees of the British Journal of Anaesthesia 2005. All rights reserved.