内源性和外源性神经类固醇对酒精依赖和攻击行为大鼠记忆的调节作用

N. Levicheva, A. Titkova, D. Bevzyuk, O. Berchenko
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引用次数: 0

摘要

酗酒和长期压力会导致认知功能受损,而认知功能尤其受神经类固醇激素的调节。外源性服用黄体酮是影响大脑荷尔蒙和神经递质调节系统的方法之一。本研究探讨了鼻内注射低剂量黄体酮对有酒精依赖和攻击行为的雄性大鼠工作记忆和空间记忆的内源性神经类固醇调节的影响。雄性大鼠的酒精依赖模型是在30天内自愿摄入浸泡在乙醇溶液中的面包,剂量为1.2克/千克。大鼠的攻击性是通过感觉接触法和 "分区 "测试确定的。为了研究大鼠的记忆过程,使用了神经伦理学方法来测试工作记忆(识别新物体)和空间记忆(巴恩斯迷宫中的定向)。每只大鼠鼻内注射孕酮的剂量为 80 微克,连续注射 10 天。使用酶联免疫吸附测定试剂盒测定大鼠额叶新皮层(FC)、海马和血清中的孕酮、睾酮和皮质醇水平。研究发现,酗酒对具有攻击行为的雄性大鼠的空间记忆和工作记忆有刺激作用。在神经类固醇失衡的背景下,长期饮酒背景下的动物社会冲突会导致物体识别和空间定向能力受损:FC、海马和血清中的孕酮和睾酮含量降低,而这些结构中的皮质醇水平升高。给有酒精依赖和攻击行为的大鼠鼻内注射黄体酮,可以抵消对抗关系对工作记忆过程的负面影响,将获得的经验恢复到基线(然而,对象分化过程仍然减弱);改善空间记忆。黄体酮对记忆的有利影响伴随着大脑结构中激素影响失衡的减少,在压力引起的糖皮质激素活性减弱的背景下,FC、海马和血清中的黄体酮和睾酮浓度得到恢复。因此,鼻内注射低剂量黄体酮能改善有酒精依赖和攻击行为的雄性大鼠的工作记忆和空间记忆,这是因为黄体酮能恢复负责记忆的大脑结构中激素(黄体酮、睾酮、皮质醇)的平衡。
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ENDOGENOUS AND EXOGENOUS NEUROSTEROIDAL MODULATION OF MEMORY IN RATS WITH ALCOHOL DEPENDENCE AND AGGRESSIVE BEHAVIOR
Alcoholism and chronic stress lead to impaired cognitive functions, which are regulated, in particular, by neurosteroid hormones. Exogenous administration of progesterone is one of the ways to influence the brain system of hormonal and neurotransmitter regulation. The effect of intranasal administration of low doses of progesterone on endogenous neurosteroid modulation of working and spatial memory in male rats with alcohol dependence and aggressive behavior was investigated. Alcohol dependence in male rats was modeled by voluntary intake of bread soaked in ethanol solution at a dose of 1.2 g/kg for 30 days. Aggressiveness was determined using the sensory contact method and the “partition” test. To study memory processes in rats, neuroethological methods of testing working (recognition of new objects) and spatial (orientation in the Barnes maze) memory were used. Progesterone was administered intranasally at a dose of 80 μg per rat for 10 days. Progesterone, testosterone, and cortisol levels were measured in the frontal neocortex (FC), hippocampus, and serum using enzyme-linked immunosorbent assay kits. The stimulatory effect of alcoholization on spatial memory and impairment of working memory in male rats with aggressive behavior was found. Zoosocial conflict on the background of prolonged alcohol consumption leads to impaired object recognition and spatial orientation against the background of neurosteroid imbalance: a decrease in progesterone and testosterone content in the FC, hippocampus, serum, and an increase in cortisol levels in these structures. Intranasal administration of progesterone to rats with alcohol dependence and aggressive behavior offsets the negative effects of confrontational relationships on working memory processes, restores the acquired experience to the baseline (however, the processes of object differentiation remain weakened); leads to improved spatial memory. The favorable effects of progesterone on memory are accompanied by a decrease in the imbalance of hormonal influences in brain structures with the restoration of progesterone and testosterone concentrations in the FC, hippocampus and serum against the background of weakening of stress-induced glucocorticoid activity. Therefore, intranasal administration of low doses of progesterone improves working and spatial memory in male rats with alcohol dependence and aggressive behavior due to the tendency to restore the balance of hormones (progesterone, testosterone, cortisol) in the brain structures responsible for memory.
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