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 and metabolism of dopamine (DA) in the rat. striatum during halothane anaesthesia. Concentra tions were measured in microdialysates collected every 20 min and applied d irectly 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 metham phetamine, a drug of abuse, or with nomifensine, a dopamine uptake blocker and antidepressant, in combination with 0.5 or 1.5% halothane. Halothane an aesthesia did not affect the dialysate (extracellular) concentration of DA at 2.0%. By contrast, the concentrations of DA metabolites [3-methoxytyrami ne (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HV A)] increased during inhaled halothane anaesthesia in a dose-dependent mann er and recovered after anaesthesia. Halothane potentiated the ability of me thamphetamine to increase the extracellular concentration of DA when admini stered systemically, whereas only a small increase in DA accumulation was s een when methamphetamine was administered locally via the perfusate. Simila rly, the increase in extracellular DA was accentuated by systemic nomifensi ne during halothane anaesthesia, but no obvious enhancement was observed wh en it was applied locally. It has been shown that the neurotoxic effect of methamphetamine is mediated by the suboxidation of DA released from the cyt oplasm into the extracellular space and transformed into highly reactive fr ee radicals. On the basis of our results, it is suggested that care should be exercised when halothane anaesthesia is used in patients abusing phenyle thylamines (amphetamines) or being treated with DA uptake blockers (nomifen sine).