褪黑素对吗啡依赖催促戒断大鼠不同脑区谷氨酸和γ-氨基丁酸含量的影响

EFFECT OF MELATONIN ON GLUTAMATE AND GAMMA-AMINOBUTYRIC ACID LEVELS IN VARIOUS REGIONS IN BRAIN OF MORPHINE WITHDRAWAL RATS

目的观察褪黑素(melatonin,MT)对吗啡催促戒断大鼠不同脑区谷氨酸(glutamate,Glu)和γ-氨基丁酸(gamma-aminobutyric acid,GABA)水平变化的影响。方法以剂量递增法连续5 d背部皮下注射盐酸吗啡复制慢性吗啡依赖模型。实验分生理盐水对照组(normal saline,NS)、吗啡依赖组(morphine,MOR)、催促戒断组(naloxone,NAL)和褪黑素治疗组(MT组),采用高效液相色谱法(high performance liquid chromatograph,HPLC)测定大鼠脑桥、中脑、海马、间脑和纹状体Glu和GABA含量。结果与NS组相比,MOR组大鼠脑桥Glu含量明显升高(P<0.01)而中脑、海马、间脑和纹状体则未见明显变化,脑桥、中脑、间脑和纹状体GABA含量明显升高(P<0.05,P<0.01);NAL组脑桥、中脑、海马、间脑和纹状体Glu含量进一步显著升高(P<0.05,P<0.01),而GABA含量则迅速下降(P<0.05,P<0.01);与NAL组相比,MT抑制吗啡催促戒断大鼠脑内Glu水平的升高(P<0.05,P<0.01)和GABA水平的下降(P<0.05,P<0.01)。结论MT对吗啡依赖纳洛酮催促戒断大鼠不同脑区的Glu和GABA水平具有调节作用。

Objective To investigate the effect of melatonin（MT） on the levels of glutamate （Glu） and gamma-aminobutyric acid （GABA）in the brain of morphine withdrawal rats. Methods Morphine dependent model in rats was induced by subcutaneous injection of morphine in daily increasing doses for 5 days. The levels of Glu and GABA in the pons, midbrain, hippocampus, diencephalons and corpus striatum were assayed with high performance liquid chromatography. Results As compared with normal saline（NS） group, the Glu level of pons in morphine（MOR） group was markedly increased（ P〈0.01）, while the GABA levels of pons, midbrain, diencephalons and corpus striatum were all increased （P〈0.05, P 〈0.01, respectively）. In naloxone （NAL） group, the Glu levels of pons, midbrain, diencephalons, hippocampus and corpus striatum were markedly increased（ P〈0.05, P〈0.01）, whereas the GABA levels of these brain regions were decreased（ P〈0.05, P〈0.01）. In MT group the Glu level markedly decreased（P 〈0.05, P〈0.01）, the GABA level increased as compared with NAL group（ P 〈0.05, P 〈0.01）. Conclusion MT could regulate the Glu and GABA levels in some involved brain regions of morphine withdrawal rats.