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INTRODUCTION: Compounds acting via metabotropic glutamate (mGlu) receptors, exhibit antidepressant activity. Moreover, development of depressive-like behavior in mice is accompanied by elevated level of prostaglandins. In our earlier study, augmentation of antidepressant-like effects of MTEP by NS398 was presented. AIM(S): The aim of this research was to verify the involvement of serotoninergic(5-HT) system in this interaction. METHOD(S): C57Bl/6J male mice were co-treated with MTEP(1 mg/kg; i.p.) and NS398 (3 mg/kg; i.p.) for 7 or 14 days. 24 h after last injection, hippocampus(Hp) and prefrontal cortex(pFC) were collected. The tissue 5-HT and 5-HIAA levels were measured using P680 HPLC system(Dionex, Sunnyvale, CA, USA). Data presented as the mean ±SEM, using one-way ANOVA(n=7–9, Newman-Keuls test), p<0.05 was considered as statistically significant. RESULTS: 14 days co-administration of MTEP with NS398 resulted in statistical significant increase (by 48%) of 5-HT level in pFC [p<0.0001], comparing to the 5-HT level observed after 7 days of administration. Similar picture (increase by 47%) was observed in pFC in 5‑HIAA level [p<0.01]. Quite different picture of changes was observed in Hp, as 5‑HT level was significantly decreased (by 36%) between 7 and 14 days of co-administration of both MTEP with NS398 [p<0.01]. 5-HT:5-HIAA turnover in pFC and Hp, comparing 7 vs. 14 days of co-treatment MTEP with NS398, showed no significant changes[ns]. CONCLUSIONS: Our findings revealed that, chronic co‑treatment MTEP with NS398 affects 5‑HT level in examined brain structures of mice. Observed effect was without changes in 5-HT:5-HIAA turnover, between 7 and 14 days of administration, in pFC and HP of C57Bl/6J mice. This kind of modulation of 5-HT system maybe interesting in the field of psychopharmacology. Further studies are necessary to determine the precise mechanism of interaction of mentioned pathways. FINANCIAL SUPPORT: Study supported by grant UMO-2014/13/D/NZ7/00292.
Single administration of zinc evokes pharmacological behavioral effects in rodents, while no brain zinc alterations were detected. The aim of the present study was to examine the effect of a single zinc hydroaspartate intraperitoneal (ip) administration on the extracellular (synaptic) zinc concentration in the rat prefrontal cortex. We used anodic stripping voltammetric (ASV) method of zinc determination in microdialysate, which assays the extracellular zinc concentration. We report that acute (65 mg/kg) zinc hydroaspartate administration (ip) increases the extracellular zinc by 48% in the rat prefrontal cortex. These data for the first time demonstrate: 1) utility of ASV zinc detection in brain microdialysates and 2) that single ip zinc administration increases brain (cortical) extracellular zinc pool. The results indicate zinc-induced fast brain penetration and may explain its rapid pharmacological effects.
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