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.