Frankel P S, Harlan R E, Garcia M M
Department of Anatomy, Tulane University School of Medicine, SL 49, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
Brain Res. 1999 Jul 24;835(2):204-12. doi: 10.1016/s0006-8993(99)01579-6.
Previous studies from this laboratory have demonstrated that acute, systemic administration of morphine results in an induction of the immediate-early gene (IEG) proteins, c-Fos and Jun-B, in the dorsomedial portion of the rat caudate-putamen (CPu). These studies have also shown that morphine can induce c-Fos in the central medial nucleus of the thalamus (CM). To determine whether this response is altered in post-dependent rats, twice-daily injections of an ascending dose of morphine were administered for 5 days, followed by a withdrawal period of 7 or 14 days. A challenge injection of morphine (10 mg/kg) was administered on the last day of withdrawal. As compared to an acute dose of morphine in a naive animal, the induction of c-Fos was increased in the dorsolateral CPu following challenge injection at 7 days, but not at 14 days. Induction of c-Fos in the CM following the challenge injection was blunted following 7 day, but not at 14 days, of withdrawal. An increase in the IEG protein, Jun-B, was also seen following 7 but not 14 days of withdrawal in both the dorsomedial and dorsolateral CPu. These findings demonstrate that a chronic treatment of morphine can result in altered patterns of IEG expression upon challenge with acute morphine, in a time-dependent manner, within the rat CPu and CM.
该实验室先前的研究表明，急性全身给予吗啡会导致大鼠尾状核-壳核（CPu）背内侧部分的即刻早期基因（IEG）蛋白c-Fos和Jun-B的诱导。这些研究还表明，吗啡可诱导丘脑中央内侧核（CM）中的c-Fos。为了确定这种反应在依赖后大鼠中是否改变，每天两次注射递增剂量的吗啡，持续5天，随后有7天或14天的戒断期。在戒断的最后一天给予一次吗啡激发注射（10mg/kg）。与未接触过吗啡的动物给予急性剂量吗啡相比，在7天而非14天的激发注射后，背外侧CPu中c-Fos的诱导增加。在7天而非14天的戒断后，激发注射后CM中c-Fos的诱导减弱。在背内侧和背外侧CPu中，戒断7天而非14天后，IEG蛋白Jun-B也增加。这些发现表明，吗啡的慢性治疗可导致在大鼠CPu和CM内，急性吗啡激发后IEG表达模式以时间依赖的方式发生改变。
