Chieng B, Williams J T
The Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201, USA.
J Neurosci. 1998 Sep 1;18(17):7033-9. doi: 10.1523/JNEUROSCI.18-17-07033.1998.
The nucleus accumbens is a key component of the reward pathway that plays a role in addiction to many drugs of abuse, including psychostimulants and opioids. The effects of withdrawal from chronic morphine were examined in the nucleus accumbens using brain slices from morphine-treated animals. Recordings were made from interneurons in the shell of nucleus accumbens, and the presynaptic inhibition of GABA-A IPSCs by opioids was examined. In slices from control animals, opioids caused a maximal inhibition of 50%, forskolin increased the IPSC amplitude by less than twofold, and the maximal inhibition by opioids in the presence of forskolin was not changed. During withdrawal, however, forskolin caused approximately a fourfold increase in the amplitude of the IPSC, and the maximal inhibition by opioids was increased to 80%. The results indicate that transmitter release is increased during opioid withdrawal, particularly after the activation of adenylyl cyclase. The cAMP-dependent increase in transmitter release is potently inhibited by opioids, such that the overall effect of opioids is augmented during withdrawal. The induction of an opioid-sensitive cAMP-dependent mechanism that regulates transmitter release may be a critical component of acute opioid withdrawal.
伏隔核是奖赏通路的关键组成部分，在对包括精神兴奋剂和阿片类药物在内的多种滥用药物成瘾过程中发挥作用。利用吗啡处理动物的脑片，在伏隔核中研究了慢性吗啡戒断的影响。从伏隔核壳部的中间神经元进行记录，并检测阿片类药物对GABA-A抑制性突触后电流（IPSCs）的突触前抑制作用。在对照动物的脑片中，阿片类药物引起的最大抑制率为50%，福斯高林使IPSC幅度增加不到两倍，且在福斯高林存在的情况下阿片类药物的最大抑制作用未改变。然而，在戒断期间，福斯高林使IPSC幅度增加约四倍，阿片类药物的最大抑制作用增加到80%。结果表明在阿片类药物戒断期间，尤其是在腺苷酸环化酶激活后，神经递质释放增加。阿片类药物能有效抑制由环磷酸腺苷（cAMP）依赖性增加的神经递质释放，使得在戒断期间阿片类药物的总体作用增强。诱导一种调节神经递质释放的阿片类药物敏感的cAMP依赖性机制可能是急性阿片类药物戒断的关键组成部分。
