Acid Release In Striatum Research Articles

Effect of amphetamine on extracellular concentrations of amino acids in striatum in neurotensin subtype 1 and 2 receptor null mice: A possible interaction between neurotensin receptors and amino acid systems for study of schizophrenia

Neurotensin (NT) is a tridecapeptide that acts as a neuromodulator in the central nervous system mainly through two NT receptors: NTS1 and NTS2. The present study was done to determine the roles of NTS1 and NTS2 on amino acid release in striatum with the use of NTS1 or NTS2 knockout ((-/-)) mice given d-amphetamine. Both NTS1(-/-) and NTS2(-/-) mice had lower extracellular concentrations of D-serine in striatum than did wild type (WT) mice. NTS2(-/-) but not NTS1(-/-) mice also had significantly lower basal concentrations of glutamate in striatum as compared to that for WT mice. Systemic administration of d-amphetamine (4 mg/kg, ip) increased glutamate release by 500% in WT mice, as compared to 300% in NTS2(-/-) mice, and 250% in NTS1(-/-) mice. Additionally, d-amphetamine injection caused a 4-fold increase in GABA release in both WT and NTS2(-/-) mice, but only a 2-fold increase in NTS1(-/-) mice. Therefore, NTS1 and NTS2 modulate basal release of D-serine and glutamate, and also d-amphetamine-induced GABA and glutamate release in striatum. These results provide further support for the involvement of NT receptors in the pathogenesis of schizophrenia and provide a better understanding of the imbalance of amino acid systems through investigation of a DA-based animal model.

Effect of drug-induced ascorbic acid release in the striatum and the nucleus accumbens in hippocampus-lesioned rats

The mechanism of ethanol, morphine, methamphetamine (MAP), and nicotine-induced ascorbic acid (AA) release in striatum, and nucleus accumbens (NAc) is not well understood. Our previous study showed that the glutamatergic system was involved in the addictive drug-induced AA release in NAc and striatum. Furthermore, frontal decortication eliminates drug-induced ascorbic acid release in the striatum but not in the NAc. In the present study, the roles of the hippocampus in drug-induced AA release in the striatum and NAc were studied by using microdialysis coupled to high performance liquid chromatography with electrochemical detection (HPLC-ECD). Ethanol (3.0 g/kg, i.p.), methamphetamine (3.0 mg/kg, i.p.), and nicotine (1.5 mg/kg, i.p.) significantly stimulated AA release in the striatum and NAc, respectively. Morphine (20 mg/kg, i.p.) significantly stimulated AA release in the striatum, but not in the NAc. After hippocampal lesion by kainic acid, AA release induced by ethanol, methamphetamine, and nicotine could be eliminated in NAc, but not in the striatum. These results suggest that the hippocampus might be a common and necessary area in addictive drug-induced AA release in the NAc, which also imply that different pathways might be involved in drug-induced AA release in the striatum and the NAc of the rats.

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.

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.

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.

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.

Potentiation by Kainate of Excitatory Amino Acid Release in Striatum: Complementary In Vivo and In Vitro Experiments

The effect of kainate on extracellular levels of amino acids in corpus striatum was investigated in vitro and in vivo, to elucidate the mechanism underlying its neurotoxicity. Kainate increased extracellular glutamate and aspartate in both striatal slices in vitro and intact striatum in vivo, as previously reported. Both in vitro and in vivo, DL-threo-3-hydroxyaspartate increased extracellular glutamate and aspartate levels (to between 150 and 200% of basal), and also enhanced their kainate-evoked release. The action of kainate in vivo was reduced by prior frontal decortication, whereas in vitro the kainate-evoked responses were only slightly reduced by tetrodotoxin, and remained above control values. These results confirm that kainate increases extracellular glutamate and aspartate, and provide evidence that this is due to synaptic release evoked by an action on receptors on glutamatergic neurone terminals. These findings may be relevant to the understanding of epilepsy.

Kainate potentiates excitatory amino acid release in striatum

Kainate potentiates excitatory amino acid release in striatum