Antidepressant activity of fluoxetine in the zinc deficiency model in rats involves the NMDA receptor complex

作者：Doboszewska Urszula^*; Szewczyk Bernadeta; Sowa Kucma Magdalena; Mlyniec Katarzyna; Rafalo Anna; Ostachowicz Beata; Lankosz Marek; Nowak Gabriel

来源：Behavioural Brain Research, 2015, 287: 323-330.

DOI：10.1016/j.bbr.2015.03.064

• Fluoxetine
• NMDA receptor
• Zinc deficiency
• Rats
• Forced swim test

The zinc deficiency animal model of depression has been proposed; however, it has not been validated in a detailed manner. We have recently shown that depression-like behavior induced by dietary zinc restriction is associated with up-regulation of hippocampal N-methyl-D-aspartate receptor (NMDAR). Here we examined the effects of chronic administration of a selective serotonin reuptake inhibitor, fluoxetine (FIX), on behavioral and biochemical alterations (within NMDAR signaling pathway) induced by zinc deficiency. Male Sprague Dawley rats were fed a zinc adequate diet (ZnA, 50 mg Zn/kg) or a zinc deficient diet (ZnD, 3 mg Zn/kg) for 4 weeks. Then, FIX treatment (10 mg/kg, i.p.) begun. Following 2 weeks of FIX administration the behavior of the rats was examined in the forced swim test (FST) and the spontaneous locomotor activity test. Twenty four hours later tissue was harvested. The proteins of NMDAR (GluN1, GluN2A and GluN2B) or AMPAR (GluA1) subunits, p-CREB and BDNF in the hippocampus (Western blot) and serum zinc level (TXRF) were examined. Depression-like behavior induced by ZnD in the FST was sensitive to chronic treatment with FLX. ZnD increased levels of GluN1, GluN2A, GluN2B and decreased pS485-GluA1, p-CREB and BDNF proteins. Administration of FIX counteracted the zinc restriction-induced changes in serum zinc level and hippocampal GluN1, GluN2A, GluN2B and p-CREB but not BDNF or pS845-GluA1 protein levels. This finding adds new evidence to the predictive validity of the proposed zinc deficiency model of depression. Antidepressant-like activity of FIX in the zinc deficiency model is associated with NMDAR complex.

• 出版日期2015-7-1