Ethanol effects of NMDA-stimulated levels of extracellular neurotransmitters by in vivo microdialysis.
To determine whether the inhibition of NMDA receptor function by ethanol observed in vitro may be reflected in vivo, we measured the effects of ethanol administration on levels of extracellular dopamine (DA) using a microdialysis method. Rats were implanted with a guide cannula under anesthesia one week prior to placement of a microdialysis probe into the striatum. At a perfusion rate of 2 microliters/min recovery of DA from a standard solution was typically 20-25%. Basal levels of dialysate DA were approximately 0.5 pg/microliter. NMDA infusion into the striatum of an awake rat caused a concentration-dependent stimulation of extracellular DA levels. A one hour infusion of NMDA caused increases in dialysate DA from 2.3-50 fold over basal at concentrations from 0.3-10 mM. MK-801 (25 microM), AP-5 (10 microM), and DNQX (10 microM) significantly inhibited the stimulation of extracellular DA levels by 1 mM NMDA for 10 minutes. This suggests complex regulation of extracellular DA levels in the striatum by NMDA. Ethanol (0.5-3 g/kg, i.p.) did not alter the extracellular DA levels in the striatum. Furthermore, ethanol administration had no significant effects on DA levels in striatal dialysates when stimulated by infusion of 1 mM NMDA for 10 minutes. Our results suggest that ethanol's actions on extracellular DA levels in vivo in the striatum may not be predicted from a single effect of ethanol on one transmitter receptor system but depend on the integration of multiple signals in this brain region.
Gonzales
R A
RA
Department of Pharmacology, University of Texas, Austin 78712, USA.
Roper
L C
LC
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D000431:Ethanol / Q000633:toxicity*; D005110:Extracellular Space / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D016202:N-Methylaspartate / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism
D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; C056723:FG 9041; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D004298:Dopamine