足底电击诱发吗啡CPP重现大鼠杏仁核谷氨酸和GABA水平的变化

Changes in glutamate and GABA levels in rat amygdala produced by reinstatement of morphine-induced conditioned place preference by foot electric shock

目的观察足底电击诱发吗啡条件性位置偏爱(CPP)重现大鼠杏仁核中的谷氨酸(GLU)和γ-氨基丁酸(GABA)水平的变化。方法50只雄性大鼠,随机分为5组(n=10):生理盐水组(C组)、消退组(E组)、重现组Ⅰ(R1组)、重现组Ⅱ(R2组)和重现组Ⅲ(R3组)。E组、R1组、R2组和R3组腹腔注射4mg·kg-1盐酸吗啡后进行训练,每天1次,连续10 d,C组腹腔注射等容积的生理盐水。CPP测试判断CPP形成后,给予7 d的消退期。以足底电击诱发CPP的重现,E组给予假电击。NS组、E组和R1组于足底电击或假电击后立即断头处死大鼠,R2组和R3组分别于足底电击后1 h和4 h处死,立即取脑,分离杏仁核。采用柱前衍生．电化学检测-高效液相色谱法测定GLU和GABA含量,并计算GLU／GABA比值。结果与C组和E组比较,R1组、R2组和R3组在CPP箱伴药室中的累积停留时间延长。与C组比较,各组GLU和GABA含量降低。与E组比较,R2组GABA含量降低。R2组GLU／GABA比值高于C组、E组、R1组和R3组(P<0．05或0．01)。结论足底电击可诱发大鼠吗啡CPP的重现,杏仁核GLU和GABA递质系统特别是GABA系统在此过程中起重要作用。

Objective To investigate the changes in glutamate （Glu） and gamma-aminobutyric acid （GABA） levels in rat amygdala when morphine-induced conditioned place preference （CPP） is reinstated by shock produced by electric current passing through bottom of foot. Methods Fifty male SD rats aged 7 weeks weighing 190-210 g were randomly divided into 5 groups （ n = 10 each） ： group Ⅰ control （C） ; group Ⅱ extinction of CPP （E） ; group Ⅲ CPP reinstatedl （R1 ） ; group Ⅳ CPP reinstated2 （R2） and group Ⅴ CPP reinstated3 （R3）. In group E, R1 , R2, R3 animals were trained with morphine 4 mg· kg^- 1 once a day for 10 consecutive days in a CPP box with 2 chambers of different colors separated with a glass plate to acquire CPP. After establishment of CPP 7 days were needed for extinction. Foot electric shock was used to reinstate CPP. Sham foot electric shock was used in group E. The animals were decapitated right after （in group C, E and R1 ） 1 h （in group R2 ） or 4 h （in group R3 ） after foot shock or sham foot shock. Amygdala was removed and homogenized. The contents of Glu and GABA in amygdala were measured by HPLC-ECD with precolumn derivatization. Results 1. The accumulated time the rats spent in the drug-paired chamber was significantly longer in group R1 , R2 and R3 than in group C and E （P 〈 0.05）. 2. The contents of Glu and GABA in amygdala were significantly lower in group E, R1, R2 and R3 than in group C （P 〈 0.05 or 0.01 ）. The GABA content was significantly lower in group R2 than in group E （P 〈 0.05）. 3. The GLU/GABA ratio was significantly higher in group R2 than in group C, E, R1 and R3 （P 〈 0.05 or 0.01 ）. Conclusion The reinstatement of morphine-induced CPP can be induced successfully by foot electric shock and the Glutaminerglc and GABAergie system, especially GABAergic system may play a role in this process.