Previous studies have shown that striatumand nucleus accumbens (NAc) are two different structures inmediating addictive drug-induced ascorbic acid (AA) release. In order to further characterize the different effects of drugs-induced AA release in the striatum and NAc, in the present study, we investigated the effect of ethanol, morphine, methamphetamine, nicotine-induced AA release in these two nuclei using microdialysis coupled to high performance liquid chromatography with electrochemical detection (HPLC-ECD). All drugs were continuously perfused directly into the striatum or NAc. This study showed that local intrastriatal or intra-accumbensal perfusion of ethanol (500 μM) could increase AA release to 280, 260% in the striatum and NAc, respectively. Intra-striatal infusion of morphine (1mM), methamphetamine (250 μM) or nicotine (500 μM), reduce striatal AA release to 48, 50, 45%, respectively. While given intra-accumbensally, morphine (1mM), methamphetamine (250 μM) or nicotine (500 μM) increase AA release to 165, 160, 160%, respectively. These results suggested that different presynaptic or postsynaptic mechanisms might be involved in addictive drug-induced AA release in the striatum and NAc.

A new recombinant neurotoxic polypeptide ANEPIII (BmK ANEPIII) derived from Scorpion peptide, which was demonstrated with antineuroexcitation properties in animal models, was examined for its action on K+ currents in primary cultured rat hippocampal and cortical neurons using the patch clamp technique in the whole-cell configuration. The delayed rectifier K+ current (Ik) was inhibited by externally applied recombinant BmK ANEPIII, while the transient A-current (IA) remained virtually unaffected. BmK ANEPIII 3 μM, reduced the delayed rectifier current by 28.2% and 23.6% in cultured rat hippocampal and cortical neurons, respectively. The concentration of half-maximal block was 155.1 nM for hippocampal neurons and 227.2 nM for cortical neurons, respectively. These results suggest that BmK ANEPIII affect K+ currents, which may lead to a reduction in neuronal excitability.

In the present study, we investigated the effect of morphine on the extracellular levels of glutamate in the anterior cingulate cortex (ACC) in freely moving rats using in vivo microdialysis coupled to high performance liquid chromatography and electrochemical detection. The results showed that either acute or chronic morphine treatment decreased the extracellular levels of glutamate in the ACC. Naloxone could reverse the decrease induced by chronic morphine treatment. The present study provided the first neurochemical evidence that morphine decreased extracellular levels of glutamate in the ACC, suggesting that glutamate in ACC is involved in the central actions of morphine.

The mechanism of morphine-, methamphetamine-, and nicotine-induced ascorbic acid (AA) release in the striatum and nucleus accumbens (NAc) is not well understood. In the present study, the roles of the corticostriatal and corticoaccumbens pathways in drug-induced AA release were studied by using microdialysis coupled to high performance liquid chromatography with electrochemical detection (HPLC-ECD). The results showed that morphine (20 mg/kg), methamphetamine (3.0 mg/kg), or nicotine (1.5 mg/kg) intraperitoneally (i.p.) significantly stimulated AA release in the striatum to more than 180%, 190%, and 140% compared with saline groups, respectively. These effects could be completely eliminated by frontal decortication, or antagonized by MK-801 (1.0 mg/kg). Moreover, methamphetamine or nicotine also significantly induced AA release in the NAc to more than 180% and 150% compared with saline groups, respectively. However, these effects could not be eliminated by frontal decortication. Although the effects of methamphetamine or nicotine in the NAc could be antagonized by MK-801, two-way ANOVA analysis did not show a significantly interaction between MK-801 and methamphetamine, or nicotine. The results indicates that the corticostriatal glutamatergic pathway may be a common and necessary pathway in drug-induced AA release in the striatum, but the corticoaccumbens glutamatergic pathway may not be crucial in drug-induced AA release in the NAc. The present study implies that different mechanisms might be involved in drug-induced AA release in the striatum and the NAc in rats.

Upon activation, brain macrophages, the microglia, release proinflammatory mediators that play important roles in eliciting neuroinflammatory responses associated with neurodegenerative diseases. As resveratrol, an antioxidant component of grape, has been reported to exert anti-inflammatory activities on macrophages, we investigated its effects on the production of TNF-alpha (TNF-α) and nitric oxide (NO) by lipopolysaccharide (LPS)-activated microglia. Exposure of cultured rat cortical microglia and a mouse microglial cell line N9 to LPS increased their release of TNF-α and NO, which was significantly inhibited by resveratrol. Further studies revealed that resveratrol suppressed LPS-induced degradation of IκBα, expression of iNOS and phosphorylation of p38 mitogen-activated protein kinases (MAPKs) in N9 microglial cells. These results demonstrate a potent suppressive effect of resveratrol on proinflammatory responses of microglia, suggesting a therapeutic potential for this compound in neurodegenerative diseases accompanied by microglial activation.