Unit II, Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343 Kraków, Poland.
Laboratory of Pharmacology and Brain Biostructure, Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343 Kraków, Poland.
Int J Mol Sci. 2023 Dec 20;25(1):100. doi: 10.3390/ijms25010100.
The pathophysiology of depression is related to the reduced volume of the hippocampus and amygdala and hypertrophy of the nucleus accumbens. The mechanism of these changes is not well understood; however, clinical studies have shown that the administration of the fast-acting antidepressant ketamine reversed the decrease in hippocampus and amygdala volume in depressed patients, and the magnitude of this effect correlated with the reduction in depressive symptoms. In the present study, we attempted to find out whether the psychedelic substance psilocybin affects neurotransmission in the limbic system in comparison to ketamine. Psilocybin and ketamine increased the release of dopamine (DA) and serotonin (5-HT) in the nucleus accumbens of naive rats as demonstrated using microdialysis. Both drugs influenced glutamate and GABA release in the nucleus accumbens, hippocampus and amygdala and increased ACh levels in the hippocampus. The changes in D2, 5-HT1A and 5-HT2A receptor density in the nucleus accumbens and hippocampus were observed as a long-lasting effect. A marked anxiolytic effect of psilocybin in the acute phase and 24 h post-treatment was shown in the open field test. These data provide the neurobiological background for psilocybin's effect on stress, anxiety and structural changes in the limbic system and translate into the antidepressant effect of psilocybin in depressed patients.
抑郁症的病理生理学与海马体和杏仁核体积减小以及伏隔核肥大有关。这些变化的机制尚不清楚；然而，临床研究表明，快速作用的抗抑郁药氯胺酮可逆转抑郁症患者海马体和杏仁核体积的减少，并且这种效应的幅度与抑郁症状的减轻相关。在本研究中，我们试图找出迷幻物质裸盖菇素是否与氯胺酮相比会影响边缘系统的神经传递。微透析显示，裸盖菇素和氯胺酮增加了未处理大鼠伏隔核中多巴胺（DA）和血清素（5-HT）的释放。两种药物均影响伏隔核、海马体和杏仁核中谷氨酸和 GABA 的释放，并增加海马体中的 ACh 水平。在伏隔核和海马体中观察到 D2、5-HT1A 和 5-HT2A 受体密度的长期变化。在旷场试验中，裸盖菇素在急性期和治疗后 24 小时显示出明显的抗焦虑作用。这些数据为裸盖菇素对压力、焦虑和边缘系统结构变化的影响提供了神经生物学背景，并转化为抑郁症患者中裸盖菇素的抗抑郁作用。
