Halothane and isoflurane increase spontaneous but reduce the N-methyl-D-aspartate-evoked dopamine release in rat striatal slices - Evidence for direct presynaptic effects

Background: Experimental data suggest that volatile anesthetics induce sign ificant changes in extracellular dopamine concentrations in the striatum, a restricted but functionally important brain area. In the present study, th e authors used a superfused slice preparation to examine the effects of hal othane and isoflurane on both spontaneous and N-methyl-D-aspartate (NMDA)-e voked dopamine release in the striatum, and whether these effects involved actions of these anesthetics mediated by gamma-aminobutyric acid receptors in this structure. Methods: Radioactivity collected from 5-min fractions was compared in the a bsence (basal release) or presence (evoked release) of NMDA alone and combi ned with various pharmacologic or anesthetic agents in slices of the dorsol ateral striatum and synaptosomes of the whole striatum prelonged with H-3-d opamine and superfused with artificial cerebrospinal fluid. Results: In tetrodotoxin-treated striatal slices, halothane and isoflurane significantly increased dopamine basal release (EC50 = 0.33 mM and 0.41 mM for halothane and isoflurane, respectively). Both agents decreased the NMDA -evoked dopamine release in both the absence (IC50 = 0.15 mM and 0.14 mM fo r halothane and isoflurane, respectively) and presence (IC50 = 0.15 mM for both halothane and isoflurane) of tetrodotoxin in slices, and in synaptosom es (IC50 = 0.19 mM for both halothane and isoflurane). NMDA-induced dopamin e release was significantly enhanced by bicuculline, a gamma-aminobutyric a cid receptor antagonist. Halothane and isoflurane inhibitory effects on NMD A-evoked dopamine release were significantly reduced in the presence of bic uculline. Conclusion: These results indicate that halothane and isoflurane decrease t he NMDA-evoked dopamine release by acting directly at dopamine terminals in striatal slices. They support the involvement of both depression of presyn aptic NMDA receptor-mediated responses and enhancement of gamma-aminobutyri c acid receptor-mediated responses in these effects.