Halothane anesthesia enhances the effect of dopamine uptake inhibition on interstitial levels of striatal dopamine.
The anesthetic, isoflurane, has been shown to potentiate the ability of the dopamine (DA)-uptake inhibitor, nomifensine, to increase the brain interstitial dopamine level ([DA]e). Since the effect of the more commenly used anesthetic, halothane, on this system is unknown, we determined [DA]e by microdialysis in the striatum of rats, conscious or anesthetized with halothane, in the presence of the more selective DA uptake inhibitor, vanoxerine (GBR 12909), or the DA releaser, d-amphetamine. Basal [DA]e was not changed by halothane. However, in halothane-anesthetized rats, the vanoxerine (3 mg/kg i.v.)-induced DA response increased severalfold compared to the response in conscious rats. The initial peak response to d-amphetamine (1 mg/kg i.v.) did not change, but the late response (1-3 h after injection) was augmented in anesthetized rats. Halothane is believed to increase firing of DA neurons in the substantia nigra and, hence, to release striatal DA. We hypothesize that [DA]e is maintained at a normal level during the increased firing by equally increased activity of the DA transporter. However, when the DA transporter is blocked by vanoxerine, the increased DA release is unimpaired and [DA]e rises.
Fink-Jensen
A
A
Department of Neurophysiology, Novo Nordisk A/S, Måløv, Denmark.
Ingwersen
S H
SH
Nielsen
P G
PG
Hansen
L
L
Nielsen
E B
EB
Hansen
A J
AJ
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D003243:Consciousness; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D005110:Extracellular Space / Q000378:metabolism; D006221:Halothane / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D010879:Piperazines / Q000097:blood / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D015102:3,4-Dihydroxyphenylacetic Acid; C043425:vanoxerine; D000661:Amphetamine; D006221:Halothane; D004298:Dopamine