Halothane enhances acetylcholine release by decreasing dopaminergic activity in rat striatal slices.
The present study investigated the effect of halothane on acetylcholine (ACh) and dopamine (DA) release from the rat striatum. Halothane decreased DA release in a concentration-dependent manner, while increased ACh release. In our previous investigation, a volatile anesthetic, halothane, inhibited DA release from the rat striatal slices in a concentration-dependent manner. Although the release of ACh from cholinergic interneurons is tonically modulated by DA in the striatum, the effect of halothane on the relationship between the release of ACh and DA has not been discussed. Using double-labeled techniques, we investigated the effect of halothane on ACh and DA release simultaneously. The slices were incubated with [14C]-choline and [3H]-DA and superfused with modified Krebs solution containing 1 microM of hemicholinium-3. We applied electrical field stimulation (2 Hz, 240 shocks), and the amount of the release of radioactivity evoked by stimulation was calculated by subtraction of the basal radioactive outflow from the total outflow at the beginning of the respective stimulation periods. The effects of drugs on the release were expressed as the ratio of stimulation-evoked fractional releases (FR), measured in the presence and absence (FRS2/FRS1) of the drug. Halothane decreased DA release in a concentration-dependent manner (FRS2/FRS1=0.767+/-0.021, 0.715+/-0.026, 0.671+/-0.014 and 0.639+/-0.033 at the concentration of 0, 0.5, 2 and 4%, respectively), while ACh release showed a biphasic change in the presence of different concentrations of halothane. The release of ACh was significantly increased at the concentration of 2%, but not at 0.5 or 4%. Halothane failed to increase the release of ACh in striatal slices after lesion by 6-OH-dopamine. The application of amphetamine reduced the release of ACh and abolished the effect of halothane. These results indicate that the effect of halothane on ACh release is indirect: it increases the release by attenuating the inhibitory effect of DA released from the nigro-striatal pathway. The nonsynaptic interaction between DA and ACh release is involved in the effect of halothane on ACh release.
Adachi
Yushi U
YU
Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, PO Box 67, H-1450, Budapest, Hungary.
Watanabe
Kazuhiko
K
Higuchi
Hideyuki
H
Satoh
Tetsuo
T
Zsilla
Gabriella
G
D000109:Acetylcholine / Q000378:metabolism*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006221:Halothane / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley
D018685:Anesthetics, Inhalation; D018492:Dopamine Antagonists; D000109:Acetylcholine; D006221:Halothane; D004298:Dopamine