Chomanic P, Karailievova L, Graban J, Jezova D
Laboratory of Pharmacological Neuroendocrinology, Department of Endocrine Regulations and Psychopharmacology, Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Dubravska cesta 9, 845 05, Bratislava, Slovakia.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia.
Cell Mol Neurobiol. 2022 Jan;42(1):137-146. doi: 10.1007/s10571-021-01067-6. Epub 2021 Mar 8.
There is some evidence that delta-opioid receptors may be involved in the brain processes related to neuroprotection. The aim of the present studies was to test the hypothesis that endogenous opioid peptides acting via delta-opioid receptors can protect against stress-induced changes in factors related to brain plasticity and stress hormone release. Forty male adult Wistar rats were used. Half of the animals were exposed to sustained partial restraint stress (hypokinesis) lasting 48 h. Rats were treated with vehicle (isotonic saline) or the delta-opioid receptor antagonist naltrindole (3 mg/kg/ml, s.c.) six times a day. The stressfulness of the model was confirmed by increased plasma concentrations of corticosterone and prolactin, the increase in anxiety behavior in the open field test, as well as the reduction of BrdU incorporation into newly formed DNA in the hippocampus. Treatment with naltrindole potentiated the stress-induced rise in aldosterone concentrations. The blockade of delta-opioid receptors resulted in a decrease in hippocampal BDNF gene expression independently of control or stress conditions. Treatment with naltrindole enhanced plasma concentrations of copeptin, a stable precursor of vasopressin. In conclusion, these results suggest that endogenous opioid peptides might play an inhibitory role in aldosterone release under stress conditions and in the control of vasopressin release independently of stress exposure. Endogenous opioids might stimulate hippocampal gene expression of the important neurotrophic factor BDNF via delta-opioid receptors.
有证据表明δ-阿片受体可能参与了与神经保护相关的大脑过程。本研究的目的是检验以下假设:通过δ-阿片受体起作用的内源性阿片肽可以抵御应激诱导的与大脑可塑性和应激激素释放相关的因子变化。使用了40只成年雄性Wistar大鼠。一半的动物接受持续48小时的部分限制应激(运动减少)。大鼠每天接受6次载体(等渗盐水)或δ-阿片受体拮抗剂纳曲吲哚(3mg/kg/ml,皮下注射)治疗。模型的应激性通过皮质酮和催乳素血浆浓度的升高、旷场试验中焦虑行为的增加以及海马体中新形成DNA中BrdU掺入的减少得以证实。纳曲吲哚治疗增强了应激诱导的醛固酮浓度升高。δ-阿片受体的阻断导致海马体BDNF基因表达下降,与对照或应激条件无关。纳曲吲哚治疗提高了copeptin(血管加压素的稳定前体)的血浆浓度。总之,这些结果表明内源性阿片肽可能在应激条件下醛固酮释放以及独立于应激暴露的血管加压素释放控制中发挥抑制作用。内源性阿片类物质可能通过δ-阿片受体刺激重要神经营养因子BDNF的海马体基因表达。