Halothane anesthesia affects NMDA-stimulated cholinergic and GABAergic modulation of striatal dopamine efflux and metabolism in the rat in vivo.
Microdialysis of the striatum of halothane-anesthetized rats was used to study the participation of local cholinergic and GABAergic neurotransmission in NMDA receptor-modulated striatal dopamine release and metabolism. Reverse dialysis.of NMDA (1 mM) evoked a 10-fold increase in dopamine efflux and reduced DOPAC and HVA to > 20% of basal values. The effect of NMDA on dopamine efflux was abolished by atropine (10 microM) but unaffected by (+)-bicuculline (50 microM). NMDA-induced decrease in DOPAC (but not HVA) efflux was potentiated by atropine, whereas (+)-bicuculline attenuated the decrease in DOPAC and HVA. Compared to our previous studies in unanesthetised rats, our data suggest that halothane anesthesia alters the balance between NMDA-stimulated cholinergic and GABAergic influences on striatal dopamine release and metabolism. Differential sensitivity to halothane of NMDA receptors expressed by the neurones mediating these modulatory influences, or loss of specific NMDA receptor populations through voltage-dependent Mg2+ block under anesthesia, could underlie these observations.
Whitehead
K J
KJ
Neurodegenerative Diseases Research Centre, Hodgkin Building, Guy's King's and St. Thomas's School of Biomedical Sciences, King's College, Guy's Campus, London, United Kingdom. k.j.whitehead@bham.ac.uk
Rose
S
S
Jenner
P
P
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D001692:Biological Transport; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006221:Halothane / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D016202:N-Methylaspartate / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011950:Receptors, Cholinergic / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology*
D018685:Anesthetics, Inhalation; D011950:Receptors, Cholinergic; D011963:Receptors, GABA-A; D015102:3,4-Dihydroxyphenylacetic Acid; D016202:N-Methylaspartate; D001285:Atropine; D006221:Halothane; D004298:Dopamine; D006719:Homovanillic Acid; D001640:Bicuculline