Institute for Basic Sciences, Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran.
Department of Physiology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.
Brain Behav. 2023 Feb;13(2):e2877. doi: 10.1002/brb3.2877. Epub 2023 Jan 11.
Despite half a century of research on vitamin D (Vit. D), its link to substance abuse and dependence has only been discussed in recent decades. Evidence also shows the involvement of Vit. D in the evolution of dopaminergic neurons in the nucleus accumbens, an increase in the expression of tyrosine hydroxylase, and the regulation of dopaminergic processes. The novel idea for this work is taken from a hypothesis given about the effectiveness of Vit. D on dopamine signaling pathway. It is therefore presumed that Vit. D can be considered an effective therapeutic approach for narcotic addiction and substance abuse.
The animals were assigned into six groups (control, vehicle, Morphine [Mor.], and Vit. D [250, 500, and 1000 IU/kg, i.p.]). Following each conditioning session in a conditioned place preference (CPP) model, the animals received Vit. D. Afterward, the locomotor activity of the animals was assessed using open-field apparatus. Malondialdehyde (MDA), nitric oxide (NO), catalase (CAT), superoxide dismutase (SOD), thiol, and total antioxidant capacity (TAC) were measured in the brain. The relative DRD2 and GDNF expressions (%) were also measured in the hippocampus.
Vit. D administration after Mor. caused a significant increase in the place preference index in the acquisition phase (p < .05). Vit. D altered the oxidation/antioxidation profiles (CAT, SOD, MDA, NO, TAC, and Thiol). Vit. D was more effective than Mor. in the expression of GDNF (p < .0001); however, in the expression of DRD2, this was only the case for 1000 IU Vit. D (p < .0001).
Considering the increased place preference index induced by Mor., it can be concluded that Vit. D interacts via the oxidative pathway and DRD2-GDNF signaling to potentiate the Mor. effect.
尽管人们对半世纪以来对维生素 D(Vit. D)的研究,但它与物质滥用和依赖的联系只是在最近几十年才被讨论。证据还表明,Vit. D 参与了伏隔核中多巴胺能神经元的进化、酪氨酸羟化酶表达的增加以及多巴胺能过程的调节。这项工作的新想法来自于关于 Vit. D 对多巴胺信号通路有效性的假设。因此,可以认为 Vit. D 可以被视为治疗成瘾和物质滥用的有效方法。
动物被分为六组(对照组、载体组、吗啡[Mor.]组和 Vit. D[250、500 和 1000 IU/kg,腹腔注射]组)。在条件性位置偏好(CPP)模型中的每个条件作用后,动物接受 Vit. D。之后,使用开放式场装置评估动物的运动活性。在大脑中测量丙二醛(MDA)、一氧化氮(NO)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、巯基和总抗氧化能力(TAC)。还测量了海马中的相对 DRD2 和 GDNF 表达(%)。
Mor. 后给予 Vit. D 可显著增加获得阶段的位置偏好指数(p<.05)。Vit. D 改变了氧化/抗氧化谱(CAT、SOD、MDA、NO、TAC 和 Thiol)。Vit. D 在 GDNF 表达方面比 Mor. 更有效(p<.0001);然而,在 DRD2 的表达方面,只有 1000 IU Vit. D 才如此(p<.0001)。
考虑到 Mor. 引起的位置偏好指数增加,可以得出结论,Vit. D 通过氧化途径和 DRD2-GDNF 信号相互作用增强了 Mor. 的作用。