期刊
BEHAVIOURAL PHARMACOLOGY
卷 27, 期 4, 页码 384-392出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FBP.0000000000000211
关键词
glutamate; Ilex paraguariensis hydroalcoholic extract; L-arginine-nitric oxide; methylxanthines; mouse; N-methyl-D-aspartate receptor; tail suspension test
资金
- Fundacao de Amparo a Pesquisa e Inovacao do Estado de Santa Catarina (FAPESC)
- Fundo de Apoio a Manutencao e ao Desenvolvimento da Educacao Superior (FUMDES)
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
- Fundo de Apoio a Pesquisa (FAP)
Ilex paraguariensis St. Hilaire (Aquifoliaceae) is a typical plant from South America. Preclinical studies have reported the effect of I. paraguariensis-based preparations on different alterations in the brain. This study aimed to examine the antidepressant-like and neuroprotective effects of I. paraguariensis hydroalcoholic extract (IpHE). The role of the N-methyl-D-aspartate receptor and the L-arginine-nitric oxide pathway in the IpHE antidepressant like effect was also evaluated. Using the tail suspension test, we showed that IpHE (0.1-10 mg/kg, orally) exerts an antidepressant-like effect similar to that of ketamine (1 mg/kg, intraperitoneally). The antidepressant-like effect depends on the N-methyl-D-aspartate receptor and L-arginine-nitric oxide pathway modulation as we observed a combinatory effect using subeffective doses of IpHE (0.01 mg/kg, orally) and ketamine (0.1 mg/kg, intraperitoneally) or MK-801 (0.001 mg/kg, intraperitoneally). Also, pretreatment of mice with L-arginine (750 mg/kg, intraperitoneally) abolished the antidepressant-like effect of IpHE. This effect coincides with the neuroprotective effect, given that glutamate toxicity (10 mmol/l) did not decrease cell viability in hippocampal or cortical slices from IpHE-treated mice. The chromatographic profile of IpHE showed the presence of the methylxanthines caffeine and theobromine. Administration of methylxanthines (2.7 mu g/kg) in mice produced an antidepressant-like effect, but not neuroprotection. We suggest that methylxanthines are at least in part responsible for the antidepressant-like effect of IpHE; further studies are necessary to determine the biological compounds responsible for the neuroprotective effect. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
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