Ethanol potentiates dopamine release during acute hypoxia in rat striatum.
We, and others, have previously demonstrated that N-methyl-D-aspartate (NMDA) receptor is involved in hypoxia or ischemia-mediated responses. We found that the NMDA antagonist ketamine attenuates cortical nitric oxide release during cerebroischemia. It has been reported that ethanol (EtOH) antagonizes NMDA-induced responses in various systems. In the present study, the interaction of EtOH and KCl-evoked striatal dopamine release in vivo during acute hypoxia was examined. High-speed chronoamperometric recording techniques, using Nafion-coated carbon fiber electrodes, were used to evaluate extracellular dopamine (DA) concentration in the striatum of urethane-anesthetized Sprague-Dawley rats. KCl was directly applied to the striatum to evoke release of DA. These anesthetized animals were paralyzed with d-tubocurarine and connected to a respirator to allow controlled respiration. Systemic concentrations of oxygen were altered by changing the rate of the respirator. We previously reported that lowering the respiratory rates from 90 to 20 times/min for 5 min decreased arterial PO(2) and facilitated KCl-induced DA release in the striatum. In this study, we found that application of NMDA antagonist MK801 attenuates hypoxic DA release, suggesting that NMDA receptor is involved in this hypoxic reaction. In contrast, EtOH dose dependently enhanced KCl-evoked DA release during hypoxia. To further examine the interactions of excitatory amino acid and EtOH on DA release, glutamate was locally applied to the striatum. Glutamate-induced DA release was not affected by the systemic application of EtOH. Taken together, these data suggest that EtOH enhances DA release in vivo during short-term hypoxia, possibly through mechanisms other than excitatory amino acid pathways.
Wang
Y
Y
Department of Pharmacology, National Defense Medical Center, 18 Se-Yuan Road, Taipei, Taiwan 100, Republic of China.
Chiou
A L
AL
Jeng
C H
CH
Yang
S T
ST
Lin
J C
JC
D000818:Animals; D001784:Blood Gas Analysis; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004563:Electrochemistry; D000431:Ethanol / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism*; D017072:Neostriatum / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D002492:Central Nervous System Depressants; D018691:Excitatory Amino Acid Antagonists; D000431:Ethanol; D018698:Glutamic Acid; D011189:Potassium Chloride; D016291:Dizocilpine Maleate; D004298:Dopamine