Ethanol-induced Ascorbic Acid Release Research Articles

Ethanol Similarly Induces Ascorbic Acid Release in the Prefrontal Cortex and Striatum of Freely Moving Mice

Previous studies have shown that acute systemic administration of ethanol induced striatal ascorbic acid (AA) release in mice and rats. Undercutting the prefrontal cortex completely eliminated ethanol-induced AA release in rat striatum. In the present study, in vivo brain dialysis coupled with high performance liquid chromatography (HPLC)-electrochemical detection was used to evaluate the effect of ethanol on the release of AA in the prefrontal cortex, compared to that in the striatum of freely moving mice. The results showed that ethanol (4.0 g/kg i.p.) similarly induced AA release in the prefrontal cortex and striatum of freely moving mice.

Differential effects of clozapine on ethanol-induced ascorbic acid release in mouse and rat striatum

Previous studies have shown that acute systemic administration of ethanol-induced striatal ascorbic acid (AA) release in mice and rats. In the present study, in vivo brain microdialysis coupled with high performance liquid chromatography (HPLC) with electrochemical detection (ECD) was used to comparatively evaluate the effects of clozapine on ethanol-induced AA release in mouse and rat striatum. The results showed that clozapine, at the dose of 15 mg/kg i.p., had no effect on basal AA or ethanol-induced AA release in rat striatum. The potentiating effect of clozapine on ethanol-induced striatal AA release was still observed in rats, at the higher dose of 30 mg/kg. In contrast, clozapine significantly inhibited ethanol-induced AA release in mouse striatum, at the dose of 15 and 30 mg/kg, without affecting basal AA release. The present study suggested that clozapine differentially regulated ethanol-induced AA release in the mouse and rat striatum.

Effects of clozapine, olanzapine and haloperidol on ethanol-induced ascorbic acid release in mouse striatum

The effects of clozapine, olanzapine and haloperidol on ethanol-induced striatal ascorbic acid (AA) release in mice were compared by using microdialysis coupled to high performance liquid chromatography with electrochemical detection. Ethanol (4.0 g/kg i.p.) significantly stimulated striatal AA release by about 200% of baseline in mice. Clozapine and olanzapine, two atypical neuroleptic drugs, at the dose of 1.0 mg/kg s.c., had no effect on basal AA or ethanol-induced AA release. However, both drugs, at the dose of 10 mg/kg s.c., significantly inhibited ethanol-induced AA release. In contrast, haloperidol, a typical neuroleptic drug, at the doses of 0.1–2.0 mg/kg, had no effect on both basal and ethanol-induced AA release. The present study demonstrated that similar actions were exhibited by clozapine and olanzapine, but not by haloperidol, for the regulation of ethanol-induced AA release in the mouse striatum.

Role of nitric oxide in ethanol-induced ascorbic acid release in striatum of freely moving mice

In the present study, in vivo brain microdialysis coupled with high performance liquid chromatography (HPLC) and electrochemical detection were used to evaluate the effects of either l-arginine ( l-Arg), the substrate of nitric oxide synthase (NOS), Nω-nitro- l-arginine methyl ester hydrochloride ( l-NAME), a non-selective NOS inhibitor, or sodium nitroprusside (SNP), a donor of NO, on the ethanol-induced release of ascorbic acid (AA) in the striatum of freely moving mice. Drugs were administered intrastriatally via the microdialysis probe and ethanol (2–4 g/kg) was administered intraperitoneally. The results showed that l-arginine (1–10 mg/ml) had no effect on either the basal AA contents in striatal extracellular fluid or the ethanol-induced release of AA. l-NAME (10 −4 to 10 −3 mg/ml) and SNP (10 −4 to 10 −3 mg/ml) both reduced the basal AA concentrations in striatal extracellular fluid. l-NAME significantly inhibited ethanol-induced release of AA, while SNP only had a transient inhibitory effect on the ethanol-induced release of AA. SNP significantly increased dehydroascorbic acid (DHAA) contents and DHAA/AA ratio but had no effect on the total AA contents (AA and DHAA contents) in striatal extracellular fluid, while l-NAME had no effect on DHAA contents but decreased the total AA contents in striatal extracellular fluid. Only high concentration l-NAME induced a transient increase in DHAA/AA ratio. Our results suggest that nitric oxide (NO) might not directly be involved in the mechanism of ethanol-induced release of AA in mouse striatum.

Endogenous released ascorbic acid suppresses ethanol-induced hydroxyl radical production in rat striatum

Previous studies have shown that acute systemic administration of ethanol induced ascorbic acid release in the striatum. However, the pharmacological implications of ethanol-induced striatal ascorbic acid release are unclear. In the present study, ethanol-induced extracellular changes of ascorbic acid and hydroxyl radical levels were detected in rat striatum by using brain microdialysis coupled to high-performance liquid chromatography with electrochemical detection. It was found that both in male and female rats, ethanol (3.0 g/kg, i.p.) increased striatal ascorbic acid release in the first 60 min after ethanol administration. Meanwhile, the extracellular hydroxyl radical levels, detected as 2,3- and 2,5-DHBA, were significantly decreased. However, when the ascorbic acid levels returned to the baseline, hydroxyl radical levels rebounded. Administration of dl-fenfluramine (20 mg/kg, i.p.) had no effect on the basal levels of ascorbic acid and hydroxyl radical, but significantly blocked ethanol-induced ascorbic acid release and increased hydroxyl radical levels significantly. Exogenous administration of ascorbic acid (20 mg/kg, s.c.) increased the extracellular levels of ascorbic acid in the striatum, and inhibited the increase of 2,3- and 2,5-DHBA in dl-fenfluramine plus ethanol group. These results provide first evidence that release of endogenous ascorbic acid in the striatum plays an important role in preventing oxidative stress by trapping hydroxyl radical in the central nervous system.

Failure of 5‐HT3 receptors in regulation of ethanol‐induced ascorbic acid release in rat striatum

AbstractPrevious studies have shown that the serotonergic system was involved in ethanol‐induced striatal ascorbic acid release in rats. In the present study the possible role of 5‐HT 3 receptors in ethanol‐induced striatal ascorbic acid release was investigated in rats using 5‐HT 3 antagonists ondansetron, DAU 6215 and 5‐HT 3 agonist 2‐methyl‐serotonin. Extracellular level of ascorbic acid in the striatum was determined by means of in vivo microdialysis coupled to HPLC with electrochemical detection. Ethanol (3 g/kg, i.p.) induced a significant increase in ascorbic acid release. Ondansetron (0.2 and 2.0 mg/kg, i.p.), DAU 6215 (0.06, 0.12 and 0.24 mg/kg, i.p.) and 2‐methyl‐serotonin (250 μg/rat, i.c.v.), administered 10 minutes before 0.15 M NaCl or ethanol (3 g/kg, i.p.), affect neither the basal nor the ethanol‐induced ascorbic acid release in rat striatum. 2‐Methylserotonin, at a dose of 500 μg/rat, i.c.v., increased the basal, but did not affect the ethanol‐induced ascorbic acid release in rat striatum. However, ritanserin (1 mg/kg, s.c.), a 5‐HT 2 receptor antagonist, and BIMU 8 (40 μg/rat, i.c.v.), a 5‐HT 4 agonist, significantly antagonized ethanol‐induced ascorbic acid release. These results suggest that 5‐HT 3 receptors, which form a part of cation channels, may not be involved in ethanolinduced striatal ascorbic acid release.

Differential effects of acute administration of haloperidol and clozapine on ethanol-induced ascorbic acid release in rat striatum

Antipsychotic drugs were initially considered to act predominantly through their antagonism at dopamine D 2-like receptors. However, reports have demonstrated that the typical neuroleptic drug haloperidol and the atypical neuroleptic drug clozapine showed differential actions in clinical, behavioral and biochemical studies. Since ascorbic acid has a potential usefulness in psychological therapeutics, the present study investigates the actions of these two drugs on ethanol-induced ascorbic acid release in the striatum in order to help explain the different mechanisms of these drugs. The results showed that clozapine, at the doses of 15 and 30 mg/kg, i.p., had no effect on basal ascorbic acid release. However, a synergistic tendency at a dose of 15 mg/kg and a significant synergism at a dose of 30 mg/kg were observed on ascorbic acid release when clozapine was used with ethanol. In contrast, haloperidol, at the doses of 0.5, 1.0 and 2.0 mg/kg, i.p., administered alone did not affect the basal release of striatal ascorbic acid, and when used together with ethanol had neither a potentiating nor an antagonizing effect on ethanol-induced ascorbic acid release. Chlorpromazine, a nonselective dopamine receptor antagonist, at the dose of 5 mg/kg, i.p., affected neither the basal nor the ethanol-induced ascorbic acid release. Ritanserin, a 5-HT 2 receptor antagonist, at the dose of 1 mg/kg, s.c., significantly antagonized ethanol-induced ascorbic acid release. These results demonstrate that clozapine dose-dependently potentiates the stimulatory effect of ethanol on striatal ascorbic acid release and this effect of clozapine may not be related to its dopamine D 2 receptor antagonism.

Opposite effects of sulpiride and SCH 23390 on ethanol-induced striatal ascorbic acid release in intact and 6-hydroxydopamine lesioned rats

The effects of l-sulpiride and SCH 23390 on ethanol-induced striatal ascorbic acid (AA) release in normal and 6-hydroxydopamine-lesioned rats were studied by using microdialysis coupled to high performance liquid chromatography with electrochemical detection. Ethanol (3.0 g/kg i.p.) significantly stimulated striatal AA release by 200% above the baseline in normal, 6-hydroxydopamine-lesioned, and reserpine-treated rats. l-Sulpiride, a dopamine D 2 antagonist, at the dose of 100 mg/kg i.p., decreased basal ascorbic acid release and showed an inhibitory tendency on ethanol-induced ascorbic acid release. However, at the higher dose of 200 mg/kg i.p., l-sulpiride significantly inhibited ethanol-induced ascorbic acid release in both normal and 6-hydroxydopamine-treated rats. SCH 23390, a dopamine D 1 antagonist, at the doses of 0.5 and 1.0 mg/kg i.p., potentiated ethanol-induced ascorbic acid release in normal rats. However, the potentiation of SCH 23390 on ethanol effect was not significant in 6-hydroxydopamine-treated rats at the dose of 1.0 mg/kg i.p. The present study demonstrates that opposite actions exist in the regulation of ethanol-induced ascorbic acid release in the striatum by dopamine D 1 and D 2 receptor blockade. It also suggests that the postsynaptic dopamine receptors are involved in mediation of ethanol-induced ascorbic acid release in rat striatum.

Involvement of the corticostriatal glutamatergic pathway in ethanol‐induced ascorbic acid release in rat striatum

The mechanism of ethanol-induced ascorbic acid (AA) release in striatum is not well understood. In the present work, the possible involvement of NMDA receptors in the corticostriatal pathway was studied by microdialysis coupled to high performance liquid chromatography with electrochemical detection. Ethanol (3.0 g/kg i.p.) stimulated significant striatal AA release to more than 200% above the baseline. This effect of ethanol could be partially antagonized by amantadine, a non-selective NMDA receptor antagonist and dopamine releaser, at a dose of 200 mg/kg i.p. and significantly antagonized by MK-801, a non-competitive NMDA receptor antagonist, at the doses of 0.5 and 1.0 mg/kg i.p. Furthermore, deafferentation of the glutamatergic projection from cortex to striatum by undercutting the prefrontal cortex completely eliminated ethanol-induced AA release in rat striatum. The basal level of AA in striatum could only be reduced by high doses of MK-801, but not by low doses of MK-801, amantadine or decortication. The results further confirm that NMDA receptors are involved in ethanol-induced AA release and provide the first evidence for the necessity of the activation of corticostriatal glutamatergic pathway in ethanol-induced AA release in rat striatum.

Dl-Fenfluramine inhibits ethanol-induced ascorbic acid release in rat striatum studied by microdialysis.

The effects of dl -fenfluramine, dl -5-hydroxytryptophan(5-HTP) and fluoxetine on ethanol-induced striatal ascorbic acid (AA) release in rat were studied by microdialysis coupled to high performance liquid chromatography with electrochemical detection. Ethanol (3.0 g/kg, i.p.) stimulated striatal AA release to more than 200% above the baseline. dl -Fenfluramine (20 mg/kg, i.p. or 40 mug/rat, i.c.v.), 10 min before ethanol administration, markedly inhibited ethanol-induced AA release. A similar result was also observed following dl -5-HTP (100 mg/kg, i.p.) administration. However, fluoxetine (10, 30 mg/kg, i.p.) showed no antagonistic effect on ethanol-induced AA release. The suppressing effect of dl -fenfluramine and dl -5-HTP on ethanolinduced AA release could be reversed by the 5-HT receptor antagonist cyproheptadine (10 mg/kg, s.c.). All these drugs had no effect on basal AA release. The results give a first evidence for the involvement of central serotonergic system, and suggest that differential activities may exist between dl -fenfluramine, dl -5-HTP and fluoxetine in regulating ethanol-induced AA release in rat striatum.

5-HT 1A receptors mediate inhibition of ethanol-induced ascorbic acid release in rat striatum studied by microdialysis

Our previous study showed that the serotonergic system was involved in the ethanol-induced striatal ascorbic acid release in rat. In the present study, the 5-HT 1A agonists and antagonists were used to analyze the possible mechanism of ethanol-induced ascorbic acid release in rat striatum. The results showed that ethanol (3.0 g/kg, i.p.) significantly increased striatal ascorbic acid release. Buspirone (5.0 mg/kg, s.c.), a partial agonist of 5-HT 1A receptors, and 8-OH-DPAT (0.5 mg/kg, s.c.), a selective agonist of 5-HT 1A receptors, showed no effect on basal ascorbic acid release in striatum, but both drugs significantly antagonized the ascorbic acid release induced by ethanol in striatum. WAY 100635 (0.5 mg/kg, s.c.), a selective antagonist of 5-HT 1A receptors, affecting neither the basal nor the ethanol-induced ascorbic acid release per se, antagonized the suppressing effect of 8-OH-DPAT on ethanol-induced ascorbic acid release in striatum. This study gives the first evidence that activation of 5-HT 1A receptors is involved in ethanol-induced ascorbic acid release in rat striatum.