NS398 (COX-2 INHIBITOR) potentiates the antidepressant-like effects of MTEP (MGLUR5 ANTAGONIST): Involvement of 5-HT system

• Autorzy: Stachowicz K. , Sowa-Kucma M. , Lenda T. , Misztak P. , Panczyszyn-Trzewik P. , Nowak G. , Pilc A.
• Języki publikacji: EN

Abstrakty

EN

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.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.121-122

Twórcy

autor

Stachowicz K.

• Department of Neurobiology, Institute of Pharmacology Polish Academy of Sciences, Cracow, Poland

autor

Sowa-Kucma M.

• Department of Neurobiology, Institute of Pharmacology Polish Academy of Sciences, Cracow, Poland

autor

Lenda T.

• Department of Neuropsychopharmacology, Institute of Pharmacology Polish Academy of Sciences, Cracow, Poland

autor

Misztak P.

• Department of Neurobiology, Institute of Pharmacology Polish Academy of Sciences, Cracow, Poland
• Department of Pharmacobiology Cracow, Jagiellonian University Medical College, Cracow, Poland

autor

Panczyszyn-Trzewik P.

• Department of Neurobiology, Institute of Pharmacology Polish Academy of Sciences, Cracow, Poland

autor

Nowak G.

• Department of Neurobiology, Institute of Pharmacology Polish Academy of Sciences, Cracow, Poland
• Department of Pharmacobiology Cracow, Jagiellonian University Medical College, Cracow, Poland

autor

Pilc A.

• Department of Neurobiology, Institute of Pharmacology Polish Academy of Sciences, Cracow, Poland