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

Abstract

Brain microdialysis was used to study the in vivo release and metabolism of dopamine (DA) in the rat striatum during halothane anaesthesia. Concentrations were measured in microdialysates collected every 20 min and applied directly to an on-line high-performance liquid chromatograph. Halothane was administered at concentrations of 0.5, 1.0, 1.5 and 2.0%. In another series of experiments, rats were treated intraperitoneally or locally with methamphetamine, a drug of abuse, or with nomifensine, a dopamine uptake blocker and antidepressant, in combination with 0.5 or 1.5% halothane. Halothane anaesthesia did not affect the dialysate (extracellular) concentration of DA at 2.0%. By contrast, the concentrations of DA metabolites [3-methoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)] increased during inhaled halothane anaesthesia in a dose-dependent manner and recovered after anaesthesia. Halothane potentiated the ability of methamphetamine to increase the extracellular concentration of DA when administered systemically, whereas only a small increase in DA accumulation was seen when methamphetamine was administered locally via the perfusate. Similarly, the increase in extracellular DA was accentuated by systemic nomifensine during halothane anaesthesia, but no obvious enhancement was observed when it was applied locally. It has been shown that the neurotoxic effect of methamphetamine is mediated by the suboxidation of DA released from the cytoplasm into the extracellular space and transformed into highly reactive free radicals. On the basis of our results, it is suggested that care should be exercised when halothane anaesthesia is used in patients abusing phenylethylamines (amphetamines) or being treated with DA uptake blockers (nomifensine).