Laboratory of Fear Anxiety Disorders, Institute of Life Science, Nanchang University, Nanchang, Jiangxi 330031, China.
Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi 330031, China.
Brain Res Bull. 2018 Mar;137:294-300. doi: 10.1016/j.brainresbull.2018.01.004. Epub 2018 Jan 9.
Emerging evidence indicates that loss of inhibitory tone in amygdala with its subsequent overactivation contributes to the development of multiple mental disorders such as anxiety disorders and post-traumatic stress disorder (PTSD). Harmine is a member of natural β-carboline alkaloids which can readily cross the blood brain barrier and displays significant antidepressant and anxiolytic effects in rodents. However, the underlying neurobiological mechanisms are largely unknown. Here, by using whole-cell patch clamp recordings in in vitro amygdala slices, we examined the effect of harmine on glutamatergic and GABAergic transmission onto basal amygdala (BA) projection neurons (PNs). Our results showed that harmine affected neither the amplitude nor the frequency of spontaneous and miniature excitatory postsynaptic currents (sEPSCs/mEPSCs) of PNs. By contrast, it markedly increased both the amplitude and frequency of the spontaneous inhibitory postsynaptic currents (sIPSCs). For mIPSCs, only an increase of their frequency but not amplitude was observed following harmine perfusion, suggesting that harmine might act through presynaptic mechanism. In parallel, a reduction of paired-pulse ratio of evoked IPSCs emerged in the presence of harmine. Furthermore, the intrinsic excitability of PNs was dramatically decreased upon harmine treatment. Together, our study suggests that harmine selectively potentiates the inhibitory but not excitatory transmission onto BA PNs, which may contribute to its antidepressant and anxiolytic influence.
新出现的证据表明，杏仁核抑制性调减退失及其随后的过度激活，导致了多种精神障碍的发展，如焦虑症和创伤后应激障碍（PTSD）。色胺是天然β-咔啉生物碱的一种，很容易穿过血脑屏障，在啮齿动物中表现出显著的抗抑郁和抗焦虑作用。然而，其潜在的神经生物学机制在很大程度上还不清楚。在这里，我们通过在体外杏仁核切片上进行全细胞膜片钳记录，研究了色胺对谷氨酸能和 GABA 能传递到基底杏仁核（BA）投射神经元（PNs）的影响。我们的结果表明，色胺既不影响 PNs 的自发性和微小兴奋性突触后电流（sEPSC/mEPSC）的幅度，也不影响其频率。相比之下，它显著增加了自发性抑制性突触后电流（sIPSC）的幅度和频率。对于 mIPSCs，只有在色胺灌注后，其频率增加，而幅度没有增加，这表明色胺可能通过突触前机制起作用。同时，在存在色胺的情况下，诱发 IPSC 的成对脉冲比减小。此外，PNs 的内在兴奋性在色胺处理后显著降低。综上所述，我们的研究表明，色胺选择性增强了对 BA PNs 的抑制性而不是兴奋性传递，这可能有助于其抗抑郁和抗焦虑作用。
