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Oxytocin regulates changes of extracellular glutamate and GABA levels induced by methamphetamine in the mouse brain

机译：催产素调节甲基苯丙胺在小鼠脑中诱导的细胞外谷氨酸和GABA水平的变化

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Oxytocin (OT), a neurohypophyseal neuropeptide, affects adaptive processes of the central nervous system. In the present study, we investigated the effects of OT on extracellular levels of glutamate (Glu) and γ-aminobutyric acid (GABA) induced by methamphetamine (MAP) in the medial prefrontal cortex (mPFC) and dorsal hippocampus (DHC) of freely moving mice, using in vivo microdialysis coupled to high-performance liquid chromatography and fluorescence detection. The results showed that OT had no effect on basal Glu levels, but attenuated MAP-induced Glu increase in the mPFC and decrease in the DHC. OT increased the basal levels of extracellular GABA in mPFC and DHC of mice, and inhibited the MAP-induced GABA decrease in DHC. Western blot results indicated that OT significantly inhibited the increased glutamatergic receptor (NR1 subunit) levels in the PFC after acute MAP administration, whereas OT further enhanced the elevated levels of glutamatergic transporter (GLT1) induced by MAP in the hippocampus of mice. Atosiban, a selective inhibitor of OT receptor, antagonized the effects of OT. The results provided the first neurochemical evidence that OT, which exerted its action via its receptor, decreased Glu release induced by MAP, and attenuated the changes in glutamatergic neurotransmission partially via regulation of NR1 and GLT1 expression. OT-induced extracellular GABA increase also suggests that OT acts potentially as an inhibitory neuromodulator in mPFC and DHC of mice.
机译：催产素（OT）是一种神经下垂神经肽，会影响中枢神经系统的适应性过程。在本研究中，我们研究了OT对甲基苯丙胺（MAP）诱导的内侧前额叶皮层（mPFC）和背侧海马（DHC）中的甲基苯丙胺（MAP）诱导的谷氨酸（Glu）和γ-氨基丁酸（GABA）的细胞外水平的影响小鼠，使用体内微透析结合高效液相色谱和荧光检测。结果表明，OT对基础Glu水平没有影响，但是MAP诱导的mPFC中Glu的增加减弱而DHC中的Glu减少。 OT增加了小鼠mPFC和DHC中细胞外GABA的基础水平，并抑制了MAP诱导的DHC中GABA的降低。免疫印迹结果表明，OT显着抑制急性MAP给药后PFC中增加的谷氨酸能受体（NR1亚基）水平，而OT进一步增强MAP诱导的小鼠海马中谷氨酸能转运蛋白（GLT1）升高。 OT受体的选择性抑制剂Atosiban拮抗OT的作用。结果提供了第一个神经化学证据，OT通过其受体发挥作用，降低了MAP诱导的Glu释放，并部分地通过调节NR1和GLT1表达减弱了谷氨酸能神经传递的变化。 OT诱导的细胞外GABA的增加也表明OT可能在小鼠的mPFC和DHC中起抑制神经调节剂的作用。

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