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.

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.

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.

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 (3.0g/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 (20mg/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 (20mg/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.

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.