title: Effects of volatile anesthetics, thiopental, and ketamine on spontaneous and depolarization-evoked dopamine release from striatal synaptosomes in the rat.
abstract: BACKGROUND
  Recent experimental data indicate that anesthesia is often associated with significant changes in brain concentrations of dopamine (DA), an inhibitory neurotransmitter located in restricted, but functionally important, areas such as the striatum. Whether the presynaptic DA nerve endings represent potential targets for anesthetics remains unknown. Therefore, the current study was designed to investigate the effects of volatile anesthetics, thiopental, and ketamine on both spontaneous and depolarization-evoked DA release from striatal synaptosomes in the rat.
  
  
  METHODS
  Purified striatal synaptosomes preloaded with 3H-DA were superfused with artificial cerebrospinal fluid (1 ml/min). Radioactivity obtained from 1-ml fractions was measured over 15 min; first, in the absence of any treatment (spontaneous release), then in either the absence (time-dependent control) or presence (evoked-release) of anesthetic and pharmacologic agents, and finally, again, without any pharmacologic stimulation. The compounds tested were: potassium chloride (15 and 50 mM), glutamate, N-methyl-D-aspartate (NMDA) and kainate (10(-4) M and 10(-3) M), MK-801 (10(-4) M, an antagonist of NMDA receptors) and 6-cyano-7-nitro-quinoxaline-2,3-dione (10(-4) M, an antagonist of D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate [AMPA] receptors), halothane, enflurane, isoflurane (1, 1.5, and 2 minimum alveolar concentrations), ketamine (10(-5) and 10(-4) M), and thiopental (10(-5) and 10(-4) M).
  
  
  RESULTS
  Volatile anesthetics induced a significant, concentration-related increase in spontaneous 3H-DA release, but thiopental and ketamine were ineffective. The effect of 2 minimum alveolar concentration enflurane (but not halothane or isoflurane) was significantly enhanced when a Mg(2+)-free cerebrospinal fluid was used, and was reduced by MK-801 application. Nomifensine (10(-5) M, a blocker of monoamine transporter) did not affect the 3H-DA release evoked by volatile anesthetics. Glutamate, kainate, NMDA, and potassium chloride induced a significant, dose-related, Ca(2+)-dependent 3H-DA release. Halothane and isoflurane produced a significant and concentration-related decrease in the 3H-DA peaks evoked by glutamate, kainate, and NMDA; however, enflurane significantly attenuated the glutamate- and kainate-mediated release, but enhanced that evoked by NMDA. Thiopental and ketamine (10(-4), but not 10(-5) M) significantly reduced the glutamate- and NMDA-stimulated release, but only thiopental decreased the kainate-induced effect. Furthermore, the effect of potassium chloride (15 mM) was significantly reduced by all anesthetics examined, whereas that of potassium chloride (50 mM) was unaffected.
  
  
  CONCLUSIONS
  The authors conclude that: (1) volatile anesthetics, thiopental, and ketamine exert significant changes in both spontaneous and depolarization-evoked 3H-DA release in the rat striatum; (2) enflurane uniquely enhances NMDA-receptor mediated dopamine release; and (3) the results obtained from these receptor-mediated effects (AMPA and NMDA) may apply to postsynaptic, as well as presynaptic, glutamate receptors.
authors.affiliation: Department of Anesthesiology, Hospital Bichat, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Mantz
authors.forename: C
authors.initials: C
authors.lastname: Varlet
authors.forename: J B
authors.initials: JB
authors.lastname: Lecharny
authors.forename: D
authors.initials: D
authors.lastname: Henzel
authors.forename: P
authors.initials: P
authors.lastname: Lenot
authors.forename: J M
authors.initials: JM
authors.lastname: Desmonts
mesh_terms: D000769:Anesthesia, Inhalation; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004737:Enflurane; D006221:Halothane; D007530:Isoflurane; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D013874:Thiopental / Q000494:pharmacology*
chemical_list: D007649:Ketamine; D004737:Enflurane; D007530:Isoflurane; D013874:Thiopental; D006221:Halothane; D004298:Dopamine