ascorbic-acid and 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic-acid

It was found that systemic application of ethanol induced brain ascorbate (AA) release. In order to study the mechanism of ethanol-evoked AA release, the role of brain glutamatergic neurotransmission was investigated using in vivo voltammetry in the striatum of freely moving rats. Pretreatment with L-trans-pyrrolidine-2,4-dicarboxylate (PDC, 10 nmol, i.c.v.), a glutamate (Glu) uptake blocker, potentiated ethanol (1 g/kg, intraperitoneal injection, i.p.)-evoked release of brain AA. N-methyl-D-aspartate (NMDA, 1 nmol, i.c.v.) produced a fast transient increase in extracellular AA, whereas alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA, 1 nmol, i.c.v.) produced a decrease in extracellular AA (75.8 +/- 3% of control). Kainate (KA, 1 nmol, i.c.v.) produced an initial decrease (48.7 +/- 11.7% of control) then an increase (250 +/- 68.5% of control) in extracellular AA. These results suggest that systemic administration of ethanol may affect the release or uptake of brain glutamatergic neurotransmitters which appear to regulate brain AA release. The NMDA, but not the non-NMDA, type of Glu receptor may be responsible for this regulation.

Topics: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Animals; Ascorbic Acid; Brain Chemistry; Dicarboxylic Acids; Electrophysiology; Ethanol; Excitatory Amino Acid Antagonists; Glutamates; Glutamic Acid; Injections, Intraventricular; Kainic Acid; Male; Microelectrodes; N-Methylaspartate; Neostriatum; Piperazines; Pyrrolidines; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Synaptic Transmission

The effect of the N-methyl-D-aspartate (NMDA) receptor antagonist, 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), on the ethanol-evoked release of brain ascorbate (AA) was investigated in freely moving rats using an in vivo voltammetry technique. Ethanol (1.0 g/kg, intraperitoneal injection, i.p.) increased the release of brain AA in the nucleus accumbens and striatum. Pretreatment with CPP (1 nmol, intracerebroventricular injection, i.c.v.) not only completely reversed the ethanol-evoked AA release but also reduced the concentration of extracellular AA and kept it at low level 80 min after the ethanol administration in both brain areas. However, 80 min after the treatment with CPP per se only the level of AA in the nucleus accumbens was decreased. The results suggest that ethanol-evoked release of AA probably is a self-protective mechanism against the neurotoxicity induced by ethanol in the brain, and the NMDA receptor may play an important role in this mechanism.

Topics: Animals; Ascorbic Acid; Brain Chemistry; Electrophysiology; Ethanol; Injections, Intraventricular; Male; Microelectrodes; Piperazines; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate