Sharp F R, Liu J, Nickolenko J, Bontempi B
Department of Neurology [V127], University of California at San Francisco, USA.
Behav Brain Res. 1995 Jan 23;66(1-2):225-30. doi: 10.1016/0166-4328(94)00146-7.
The c-fos and junB immediate early genes (IEGs) were induced in neurons of the medial and ventral striatum following administration of morphine. The striatal induction of c-fos and junB mRNA and Fos protein was blocked by naloxone, the D1 dopamine (DA) receptor antagonists, SCH23390 and SCH39166, and the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, MK801. SCH23390 and MK801 did not block morphine induction of c-fos and junB in septum. Since the pattern of the morphine induction of c-fos and junB in striatum and nucleus accumbens was similar to that observed with cocaine and amphetamine [2,18,45,51], these data support current concepts that limbic striatum and nucleus accumbens are among the brain regions that mediate drug abuse [9,10,23,27,49]. If it is true that D1 receptors activate the CRE (cyclase response element) and NMDA receptors activate the SRE (serum response element) in the c-fos promoter [1], then this data suggests that serial activation of mu opiate, NMDA and D1 receptors on different neurons is required to induce Fos in striatal neurons with D1 Moreover, concurrent activation of NMDA and D1 receptors is required for Fos induction in striatal neurons. The Fos induced by this simultaneous activation of NMDA and D1 receptors should lead to long-term changes of gene expression that might also be involved in changes of brain circuits that could form the basis for 'memories' relating to prior exposure to addictive drugs.
给予吗啡后，内侧和腹侧纹状体的神经元中c-fos和junB即刻早期基因（IEGs）被诱导。纳洛酮、D1多巴胺（DA）受体拮抗剂SCH23390和SCH39166以及N-甲基-D-天冬氨酸（NMDA）谷氨酸受体拮抗剂MK801可阻断纹状体中c-fos和junB mRNA以及Fos蛋白的诱导。SCH23390和MK801并不阻断吗啡对隔区c-fos和junB的诱导。由于纹状体和伏隔核中吗啡诱导c-fos和junB的模式与可卡因和苯丙胺所观察到的相似[2,18,45,51]，这些数据支持了当前的观点，即边缘纹状体和伏隔核是介导药物滥用的脑区之一[9,10,23,27,49]。如果D1受体激活c-fos启动子中的环化酶反应元件（CRE）且NMDA受体激活血清反应元件（SRE）这一说法属实[1]，那么这些数据表明，不同神经元上的μ阿片受体、NMDA受体和D1受体需依次激活才能在具有D1的纹状体神经元中诱导Fos。此外，在纹状体神经元中诱导Fos需要NMDA和D1受体同时激活。由NMDA和D1受体同时激活所诱导的Fos应会导致基因表达的长期变化，这也可能参与脑回路的改变，而这种改变可能构成与先前接触成瘾性药物相关“记忆”的基础。
