Department of Pharmacology, Shenyang Pharmaceutical University, China.
Addict Biol. 2012 Jul;17(4):758-69. doi: 10.1111/j.1369-1600.2012.00439.x. Epub 2012 Apr 16.
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.
催产素（OT）是一种神经垂体神经肽，影响中枢神经系统的适应性过程。在本研究中，我们使用体内微透析与高效液相色谱和荧光检测相结合的方法，研究了 OT 对自由活动小鼠内侧前额叶皮层（mPFC）和背侧海马（DHC）中甲基苯丙胺（MAP）诱导的细胞外谷氨酸（Glu）和γ-氨基丁酸（GABA）水平的影响。结果表明，OT 对基础 Glu 水平没有影响，但可抑制 mPFC 和 DHC 中 MAP 诱导的 Glu 增加。OT 增加了小鼠 mPFC 和 DHC 中细胞外 GABA 的基础水平，并抑制了 DHC 中 MAP 诱导的 GABA 减少。Western blot 结果表明，OT 可显著抑制急性 MAP 给药后 PFC 中谷氨酸能受体（NR1 亚基）水平的升高，而 OT 进一步增强了 MAP 在小鼠海马中诱导的谷氨酸转运体（GLT1）水平的升高。OT 受体的选择性抑制剂阿托西班拮抗了 OT 的作用。研究结果提供了第一个神经化学证据，表明 OT 通过其受体发挥作用，可降低 MAP 诱导的 Glu 释放，并通过调节 NR1 和 GLT1 的表达部分减轻谷氨酸能神经传递的变化。OT 诱导的细胞外 GABA 增加也表明，OT 可能作为小鼠 mPFC 和 DHC 中的抑制性神经调质发挥作用。
