title: Isoflurane anesthesia inhibits clozapine- and risperidone-induced dopamine release and anesthesia-induced changes in dopamine metabolism was modified by fluoxetine in the rat striatum: an in vivo microdialysis study.
abstract: Previously, we have reported that halothane anesthesia increases the extracellular concentrations of dopamine (DA) metabolites in the rat striatum using in vivo microdialysis techniques, and we have suggested that volatile anesthetics affect DA release and metabolism in various ways. The present investigation assesses the effect of isoflurane, widely used in clinical anesthesia, on DA release and metabolism. A microdialysis probe was implanted in the striatum of male Sprague-Dawley rats (n=5-7 per group). After recovery, the probe was perfused with modified Ringer's solution and 40 microl of dialysate were injected into a high performance liquid chromatograph every 20 min. The rats were given saline or the same volume of 10 mg kg(-1) clozapine, risperidone, fluoxetine or citalopram. After the pharmacological treatment, the rats were anesthetized with 1.0% or 2.5% isoflurane for 1h. The data were analyzed using two-way analysis of variance (ANOVA). For each drug with significant (p<0.05) drug-time interactions, the statistical analysis included one-way ANOVA and Newman-Keuls post hoc comparisons. A high concentration of isoflurane (2.5%) anesthesia increased the extracellular concentration of DA metabolites during emergence from anesthesia. The levels of DA metabolites increased in an isoflurane concentration-dependent manner. Isoflurane attenuated DA release induced by clozapine and risperidone. Fluoxetine, but not citalopram, antagonized the isoflurane-induced increase in metabolites. The results of current investigation suggest that isoflurane enhances presynaptic DA metabolism, and that the oxidation of DA might be partially modulated by the activities of the dopaminergic-serotonergic pathway at a presynaptic site in the rat striatum.
authors: Intensive Care Unit of University Hospital, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu city, Shizuoka 431-3192, Japan. yuadachi@poppy.ocn.ne.jp
authors: Yushi U
authors: YU
authors: Adachi
authors: Shigeyuki
authors: S
authors: Yamada
authors: Maiko
authors: M
authors: Satomoto
authors: Hideyuki
authors: H
authors: Higuchi
authors: Kazuhiko
authors: K
authors: Watanabe
authors: Tomiei
authors: T
authors: Kazama
authors: Soichiro
authors: S
authors: Mimuro
authors: Shigehito
authors: S
authors: Sato
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003024:Clozapine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D005473:Fluoxetine / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D011619:Psychotropic Drugs / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018967:Risperidone / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D018685:Anesthetics, Inhalation; D003024:Clozapine; D004298:Dopamine; D018492:Dopamine Antagonists; D005473:Fluoxetine; D007530:Isoflurane; D011619:Psychotropic Drugs; D018967:Risperidone; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors