Halothane potentiates the effect of methamphetamine and nomifensine on extracellular dopamine levels in rat striatum: a microdialysis study

Brain microdialysis was used to study the in vivo release andmetabolism of dopamine (DA) in the rat striatum during halothaneanaesthesia. Concentrations were measured in microdialysatescollected every 20 min and applied directly to an on-linehigh-performance liquid chromatograph. Halothane was administeredat concentrations of 0.5, 1.0, 1.5 and 2.0%. In another seriesof experiments, rats were treated intraperitoneally or locallywith methamphetamine, a drug of abuse, or with nomifensine,a dopamine uptake blocker and antidepressant, in combinationwith 0.5 or 1.5% halothane. Halothane anaesthesia did not affectthe dialysate (extracellular) concentration of DA at 2.0%. Bycontrast, the concentrations of DA metabolites [3-methoxytyramine(3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillicacid (HVA)] increased during inhaled halothane anaesthesia ina dose-dependent manner and recovered after anaesthesia. Halothanepotentiated the ability of methamphetamine to increase the extracellularconcentration of DA when administered systemically, whereasonly a small increase in DA accumulation was seen when methamphetaminewas administered locally via the perfusate. Similarly, the increasein extracellular DA was accentuated by systemic nomifensineduring halothane anaesthesia, but no obvious enhancement wasobserved when it was applied locally. It has been shown thatthe neurotoxic effect of methamphetamine is mediated by thesuboxidation of DA released from the cytoplasm into the extracellularspace and transformed into highly reactive free radicals. Onthe basis of our results, it is suggested that care should beexercised when halothane anaesthesia is used in patients abusingphenylethylamines (amphetamines) or being treated with DA uptakeblockers (nomifensine). Br J Anaesth 2001; 86: 837–45