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.

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.

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 15mg/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 30mg/kg. In contrast, clozapine significantly inhibited ethanol-induced AA release in mouse striatum, at the dose of 15 and 30mg/kg, without affecting basal AA release. The present study suggested that clozapine differentially regulated ethanol-induced AA release in the mouse and rat striatum.

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.

Accumulating evidence has indicated that there might exist some correlation between opiate reward and certain kinds of learning and memory processes. The present study attempted to investigate the correlation between individual differences in morphine reward and capacities in spatial learning and spontaneous alternation. In the present studies, good-response (GR) and poor-response (PR) mice were respectively selected according to their performance in a spatial learning test involving the Morris water maze or in a spontaneous alternation task using the Y-maze. In a place preference conditioning procedure, morphine (3.0 mg/kg) produced significant conditioned place preference (CPP) in both GR and PR mice selected by using either the Morris water maze or the Y-maze. The PR mice selected with the Morris water maze showed significantly more CPP induced by morphine than the GR mice. However, no detectable difference was observed in morphine-induced CPP between the GR and PR mice selected with the Y-maze. These results suggested that the variation in morphine-induced CPP in mice is somehow differentially related to that of spatial learning but unlikely to that of spontaneous alternation.