Vinpocetine Improves Scopolamine Induced Learning and Memory Dysfunction in C57 BL/6J Mice.

Vinpocetine is an inhibitor of phosphodiesterase type 1 (PDE1), which has been used for treating stroke for over 40 years. However, according to current clinical dosage and treatment period, its direct effect on memory is unclear. In this study, we investigated whether vinpocetine could reverse the scopolamine (SCO)-induced cognitive deficits in animals. Behavioral experiments, including open field, Y-maze, and fear conditioning tests were used to determine the possible role of vinpocetine on scopolamine-induced memory dysfunction. In the open field and Y-maze tests, there were significant differences between the control (CON) group and SCO group. Vinpocetine (4 mg/kg) administration for consecutive 28 d significantly improved the scopolamine-induced memory dysfunction. In the fear conditioning test, vinpocetine (2, 4 mg/kg) administration had certain beneficial effect on emotional memory. Our results suggest that vinpocetine could improve cognitive function in memory deficient mice and high clinic dosage might be better.

[Effect of dexmedetomidine on the changes of EAA and the expression of NMDA NR1 protein in hippocampus in global cerebral ischemia/reperfusion rats].

OBJECTIVE: To observe the effects of dexmedetomidine (DEX) on glutamate (Glu), aspartic acid (Asp) release and NMDAR1 expression in hippocampus in global cerebral ischemia/reperfusion rats, and investigate the protective effect and the related mechanism of neurotransmitters. METHODS: Fifty-four male Wistar rats were randomly divided into three groups (n=18):sham group(A), ischemia/reperfusion group(B), dexmedetomidine pretreatment group(C). Total cerebral ischemia model was set up by four vessel occlusion in rats. Glu and Asp levels were measured with microdialysis at different time. Then the animals were decapitated and the brains were immediately removed to detect NMDAR1 expression in hippocampus area by immunohistochemistry and Western-blot. RESULTS: Compared with that in group B, the levels of Glu, Asp and NMDA NR1 protein were significantly decreased in the dexmedetomidine pretreatment group (P<0.05 or 0.01). CONCLUSIONS: Dexmedetomidine might has a protective effect on hippocampus in global cerebral ischemia/reperfusion animals. The protective mechanism might be involved in inhibiting excitatory amino acids(EAA) release and NMDAR1 expression.

[Penehyclidine hydrochloride inhibits glutamate release and related research in global brain ischemia/reperfusion rats].

OBJECTIVE: To investigate the effect of penehyclidine hydrochloride on glutamate (Glu)release and N-methyl-D-aspartate receptor (NMDAR)1 expression in hippocampus CA1 with global cerebral ischemia/reperfusion rats. METHODS: Sixty male Wistar rats were randomly allocated into three groups; group A received sham operation; group B received ischemia/reperfusion; group C received penehyclidine hydrochloride treatment (2 mg/kg) before ischemia/reperfusion (n=20). Global cerebral ischemia was induced according to Pulsinelli-Brierley method. All animals were divided into two experiments: (I) Microdialysis plus HPLC/FD were used to detect Glu level after reperfusion 1 h, 3 h, 6 h. (II) After reperfusion 3 h, the animals were decapitated on ice and the brains were immediately removed to detect NMDAR1 expression in CA1 area by immunohistochemistry. RESULTS: After penehyclidine hydrochloride treatment, extracellular Glu level in CA1 were significantly decreased compared with those of control group (P < 0.05 or 0.01); Total integrated OD, average gray value and positive-cell area of NMDAR1 in CA1 were also significantly decreased compared with those of control group (P < 0.05 or 0.01). CONCLUSION: Penehyclidine hydrochloride might has protective effect in hippocampus CA1 on global cerebral ischemia/reperfusion animals. The protective mechanism might be involved in inhibiting Glu release and NMDAR1 expression.

Similar effects of clozapine and olanzapine on ethanol-induced ascorbic acid release in the prefrontal cortex of freely moving mice.

Previous studies have shown that acute systemic administration of ethanol induced ascorbic acid (AA) release in mouse striatum and prefrontal cortex. Clozapine and olanzapine showed similar effects on ethanol-induced AA release in mouse striatum. However, their effects on ethanol-induced AA release in mouse prefrontal cortex have not been reported. Thus, their effects on this neurochemical event were further investigated in the present study. The results showed that ethanol (4.0 gkg i.p.) significantly stimulated AA release in the prefrontal cortex by about 200 of baseline in mice. Clozapine and olanzapine, at the dose of 1.0 mgkg s.c., had no effect on basal AA or ethanol-induced AA release. However, both drugs, at the dose of 10 mgkg s.c., significantly inhibited ethanol-induced AA release. The present study demonstrated for the first time that similar actions were exhibited by clozapine and olanzapine for the regulation of ethanol-induced AA release in the mouse prefrontal cortex.

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.

Differential effects of drug-induced ascorbic acid release in the striatum and nucleus accumbens of freely moving rats.

Previous studies have shown that striatum and nucleus accumbens (NAc) are two different structures in mediating 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 microM) could increase AA release to 280, 260% in the striatum and NAc, respectively. Intra-striatal infusion of morphine (1 mM), methamphetamine (250 microM) or nicotine (500 microM), reduce striatal AA release to 48, 50, 45%, respectively. While given intra-accumbensally, morphine (1 mM), methamphetamine (250 microM) or nicotine (500 microM) 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.

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.

Frontal decortication eliminates drug-induced ascorbic acid release in the striatum but not the nucleus accumbens of freely moving rats.

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.

[Effect of high-frequency stimulation to subthalamic nucleus on STR neuronal firing rates in Parkinson disease rats].

AIM: To observe the change of STR neuronal firing rates with high frequency stimulation of subthalamic nucleus in PD rats. METHODS: A model of Parkinson's disease was induced by unilateral administration of 6-hydroxydopamine into right substantia nigra in rats. After the high-frequency stimulation to STN, the spontaneous firing rates of STR on normal and PD rats were recorded by using extracellular recordings. RESULTS: Stimulation caused a direct excited effect of STR neurons in normal rats whereas a excited and inhibited effect in PD rats. The inhibited effect was correlated with the stimulation period (r = 0.94). CONCLUSION: Stimulation to STN may inhibit the spontaneous firing rates of STR neurons in PD rats. These results also give some clues that high-frequency stimulation to STN may be a effective therapy to the clinical treatment of Parkinson's disease.