University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada.
J Psychopharmacol. 2023 Nov;37(11):1105-1115. doi: 10.1177/02698811231209235. Epub 2023 Nov 9.
Wistar Kyoto (WKY) rats manifest abnormalities in the function of monoamine receptors and transporters, as well as levels of these neurotransmitters in the brain. The present study assessed alterations in the firing activity of serotonin (5-hydroxytryptamine [5-HT]), norepinephrine (NE), and dopamine (DA) neurons, as well as the activity of 5-HT and NE receptors and transporters in the hippocampus.
In vivo electrophysiological recordings were conducted in male WKY and Wistar rats. Extracellular single-unit recordings of 5-HT, NE, and DA neurons were performed. Recordings of pyramidal neurons were conducted in the medial prefrontal cortex (mPFC) and the hippocampus, where direct application of 5-HT and NE by iontophoresis was also carried out.
The mean firing rate of 5-HT neurons was significantly decreased in WKY compared to Wistar rats. The burst activity of NE neurons was significantly increased in WKY, while their mean firing activity was not changed. There was no alteration in the firing, burst, and population activity of DA neurons in WKY animals. In the hippocampus, a decrease in sensitivity of α-adrenoceptors, but not 5-HT receptors, was observed. There was, however, no change in the activity of 5-HT and NE transporters. The firing activity of mPFC pyramidal neurons was similar in WKY versus Wistar rats.
In WKY rats, there was a decrease in the firing activity of 5-HT neurons. There was also an enhanced burst activity of NE neurons, accompanied by a reduction in sensitivity of the α-adrenoceptor in the hippocampus, inferring a decrease in NE transmission.
Wistar Kyoto(WKY)大鼠表现出单胺受体和转运体功能以及大脑中这些神经递质水平的异常。本研究评估了 5-羟色胺(5-HT)、去甲肾上腺素(NE)和多巴胺(DA)神经元放电活动的变化,以及海马体中 5-HT 和 NE 受体和转运体的活性。
在雄性 WKY 和 Wistar 大鼠中进行体内电生理记录。进行 5-HT、NE 和 DA 神经元的细胞外单细胞记录。在中前额皮质(mPFC)和海马体中进行锥体神经元的记录,其中通过离子电渗法直接应用 5-HT 和 NE。
与 Wistar 大鼠相比,WKY 大鼠的 5-HT 神经元放电率明显降低。NE 神经元的爆发活动显著增加,而其平均放电活动没有变化。WKY 动物的 DA 神经元放电、爆发和群体活动没有改变。在海马体中,观察到 α-肾上腺素能受体敏感性降低,但 5-HT 受体活性没有改变。5-HT 和 NE 转运体的活性没有变化。mPFC 锥体神经元的放电活动在 WKY 与 Wistar 大鼠之间相似。
在 WKY 大鼠中,5-HT 神经元的放电活动减少。NE 神经元的爆发活动也增强,伴随着海马体中 α-肾上腺素能受体敏感性降低,提示 NE 传递减少。