反复吗啡暴露后短期戒断时大鼠伏核大麻素CB1受体的功能变化

FUNCTIONAL CHANGES OF CB1 RECEPTOR IN RATS' NUCLEUS ACCUMBENS FOLLOWING SHORT-TERM WITHDRAWAL OF REPEATED MORPHINE EXPOSURE

目的獉獉:探索反复吗啡暴露后短期戒断时,大麻素信号对大鼠伏核中等有棘神经元接受的自发性抑制性突触后电流调节功能的变化。方法獉獉:24只SD大鼠(♂)随机分为吗啡组和对照组,并分别按10 mg.kg-1.d-1的剂量腹部皮下注射吗啡和生理盐水,连续注射7 d。在药物戒断后的d3分别制备伏核脑片,在全细胞膜片钳模式下分别记录两组大鼠伏核中等有棘神经元所接受的自发性抑制性突触后电流,观察两组电流的频率和幅度是否存在差异,以及两者对大麻素受体激动剂的反应性的异同。结果獉獉:(1)在戒断3 d后,吗啡组和对照组自发性抑制性突触后电流的幅度分别为23.40±s 3.9 pA,21.60±s 4.1 pA,两组比较无显著差异(P>0.05);频率分别是1.62±s0.47 Hz,1.46±s 0.51 Hz,二者比较无显著差异(P>0.05)。(2)灌流大麻素CB1受体激动剂WIN55,212-2后,吗啡组和对照组自发性抑制性突触后电流的幅度分别为基线水平的75.1±s 7.6(%)和93.7±s 8.4(%),两组差异显著(P<0.05);频率分别为基线水平的64.6±s 6.3(%)和89.8±s 9.7(%),两组差异显著(P<0.05)。结论獉獉:大鼠反复吗啡暴露后短期戒断时,伏核大麻素CB1受体功能发生变化,表现为其对吗啡组伏核中等有棘神经元接受的自发性抑制性突触后电流的抑制作用显著增强。

Objective： To investigate the changes in the regulation of spontaneous inhibitory postsynaptic currents（sIPSC）to the medium spiny neurons in rat nucleus accumbens by cannabinoid（CB） system during acute withdrawal after repeated morphine treatment.Methods：Rats were randomly divided into two groups：SAL group and MOR group.Rats in both groups were given seven daily sc of saline（0.9%NaCl）and morphine（10 mg·kg-1·d-1）in saline,respectively.The saline-or morphine-treated rats were killed 3 days after the last injection for electrophysiological recordings.The sIPSC was recorded in conventional whole-cell patch-clamp recording configuration under voltage-clamp mode to study the distinctions of sIPSC and their sensitivity to CB1 receptor agonist WIN55,212-2 between both groups.Results：（1）sIPSC had amplitudes indiscriminate in both groups（P0.05）：23.40±s 3.9 pA（MOR）,21.60±s 4.1 pA（SAL）.Meanwhile,the frequency of sIPSC was similar to saline-and morphine-treated rats（P0.05）：1.62±s 0.47 Hz（MOR）,1.46±s 0.51 Hz（SAL）.（2）In slices from rats received repeated treatment with morphine,the inhibitory effects of WIN55,212-2 on sIPSC frequency and amplitude were both significantly potentiated（P0.05）,with amplitude decreased to（% baseline）：93.7±s 8.4（%）（SAL）,75.1±s 7.6（%）（MOR）,and frequency decreased to（%baseline）：89.8±s 9.7（%）（SAL）,64.6±s 6.3（%）（MOR）.Conclusion：Compared to the SAL group,the inhibitory effect of activated CB1 receptor was potentiated during short-term abstinence after repeated treatment with morphine,manifesting by an enhanced inhibitory action of WIN55,212-2 on sIPSC recorded from rats exposed to morphine.