氯胺酮
原肌球蛋白受体激酶B
抗抑郁药
脑源性神经营养因子
神经营养因子
药理学
NMDA受体
海马体
生理盐水
海马结构
乙醇
内分泌学
化学
内科学
心理学
受体
医学
神经科学
生物化学
作者
Marcos Brandão Contó,Ricardo Marcos Pautassi,Rosana Camarini
出处
期刊:Neuroscience
[Elsevier]
日期:2022-06-01
卷期号:493: 1-14
被引量:1
标识
DOI:10.1016/j.neuroscience.2022.04.015
摘要
There is a high level of comorbidity between depression and alcohol use disorder. Subanesthetic doses of ketamine induce short-acting and enduring antidepressant effects after a single or a few administrations. Considering such comorbidity, we assessed, in Swiss male mice, if ketamine-induced antidepressant-like effects would alter ethanol's rewarding effects; and, if ethanol pretreatment would alter the rewarding and antidepressant effects of ketamine. The role of the brain-derived neurotrophic factor (BDNF) and its high and low affinity receptors TrkB and p75NTR, respectively, in both reward and depression-related behaviors is well established. The present study assessed, in outbred Swiss male mice, the expression of these proteins in the prefrontal cortex and hippocampus. Ketamine did not alter the development of ethanol-induced conditioned place preference (CPP), yet ethanol inhibited the expression of CPP induced by 50 mg/kg ketamine. The antidepressant action of 50 mg/kg ketamine was attenuated after repeated treatment (i.e., developed tolerance), an effect blocked by ethanol preexposure; ethanol also inhibited the antidepressant effect of 30 mg/kg ketamine. Ketamine (50 mg/kg) and Ethanol-Ketamine (50 mg/kg) groups showed lower levels of 145 kDa TrkB in the hippocampus than Saline-treated group. Ethanol-Ketamine (50 mg/kg) decreased the hippocampal expression of p75NTR compared to Saline-Saline and Saline-Ethanol groups. Ketamine (50 mg/kg) induced hippocampal downregulation of 145 kDa TrkB may contribute to ketamine-induced antidepressant tolerance. Likewise, a relationship between low hippocampal levels of p75NTR in the Ethanol-Ketamine (50 mg/kg) and ketamine-induced CPP blockade may be considered. The findings underscore potential ethanol-ketamine interactions likely to undermine ketamine putative antidepressant effects.
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