PNAS:美國(guó)耶魯大學(xué)的研究人員發(fā)現(xiàn)了氯胺酮刺激大腦的神經(jīng)機(jī)制。

日期：2015-06-09資料來(lái)源：生物質(zhì)

相關(guān)主題：

美國(guó)耶魯大學(xué)醫(yī)學(xué)院精神病學(xué)和藥理學(xué)系的一項(xiàng)研究表明，抗抑郁藥氯胺酮可以通過(guò)刺激大腦前額葉皮層的一個(gè)區(qū)域發(fā)揮作用。

氯胺酮可以產(chǎn)生迅速而長(zhǎng)效的抗抑郁藥物效果，然而這種藥物的副作用和濫用的潛力限制了它的廣泛應(yīng)用，而且氯胺酮的效應(yīng)的細(xì)胞機(jī)制尚不清楚。為了確定下邊緣前額葉皮層(IL-PFC)在氯胺酮的抗抑郁藥物作用中的作用，Ronald S. Duman及其同事調(diào)控了大鼠的下邊緣前額葉皮層(IL-PFC)神經(jīng)元的活性，并且監(jiān)測(cè)了這些大鼠的行為響應(yīng)以及神經(jīng)元結(jié)構(gòu)的變化。這組作者發(fā)現(xiàn)，下邊緣前額葉皮層(IL-PFC)區(qū)域的神經(jīng)元失去活性阻滯了系統(tǒng)的氯胺酮效應(yīng)，而在下邊緣前額葉皮層(IL-PFC)區(qū)域局部注射氯胺酮?jiǎng)t重現(xiàn)了系統(tǒng)的氯胺酮行為效應(yīng)。這組作者進(jìn)一步發(fā)現(xiàn)，對(duì)下邊緣前額葉皮層(IL-PFC)神經(jīng)元的光遺傳學(xué)刺激產(chǎn)生了類(lèi)似于氯胺酮的迅速而長(zhǎng)效的抗抑郁藥物效應(yīng)，而某些下邊緣前額葉皮層(IL-PFC)神經(jīng)元對(duì)這種刺激做出反應(yīng)而發(fā)育出了額外的突觸。氯胺酮可能刺激前額葉皮層的谷氨酸鹽的暴增，這個(gè)區(qū)域此前已被認(rèn)為在抑郁行為中起到了一種作用。這組作者說(shuō)，這些結(jié)果提示，對(duì)下邊緣前額葉皮層(IL-PFC)的進(jìn)一步研究可能幫助開(kāi)發(fā)出其他迅速而長(zhǎng)效的抗抑郁藥物療法。

原文鏈接：

Optogeneticstimulation of infralimbic PFC reproduces ketamine’s rapid and sustained antidepressant actions

原文摘要：

Ketamine produces rapid and sustained antidepressant actions in depressed patients, but the precise cellular mechanisms underlying these effects have not been identified. Here we determined if modulation of neuronal activity in the infralimbic prefrontal cortex (IL-PFC) underlies the antidepressant and anxiolytic actions of ketamine. We found that neuronal inactivation of the IL-PFC completely blocked the antidepressant and anxiolytic effects of systemic ketamine in rodent models and that ketamine microinfusion into IL-PFC reproduced these behavioral actions of systemic ketamine. We also found that optogenetic stimulation of the IL-PFC produced rapid and long-lasting antidepressant and anxiolytic effects and that these effects are associated with increased number and functionof spine synapses of layer V pyramidal neurons. The results demonstrate that ketamine infusions or optogenetic stimulation of IL-PFC are sufficient to produce long-lasting antidepressant behavioral and synaptic responses similar to the effects of systemic ketamine administration.

doi: 10.1073

作者：Manabu Fuchikami 點(diǎn)擊：次