Morphine addiction is categorized as a chronic recurrent brain disease which always results in mental disturbance, concomitant diseases and early death. Recent evidence suggested that Sirtuin 1 (SIRT1) played a crucial role in learning, memory and reward, nevertheless, its role in morphine addiction is still unclear. We explored whether SIRT1 in the ventrolateral orbital cortex (VLO) is associated with morphine addiction and its potential mechanism. We applied the morphine-induced behavioral sensitization paradigm to investigate whether microinjection of EX527, a SIRT1 inhibitor, into the VLO could affect the rat behaviors. Furthermore, we focused on the expression of extracellular signal-regulated protein kinases (ERK) and brain-derived neurotrophic factor (BDNF), potential downstream targets of SIRT1. Microinjecting EX527 into the VLO significantly suppressed morphine-induced behavioral sensitization. We found that the expression of SIRT1, phosphorylated ERK (p-ERK) and BDNF in the VLO were markedly up-regulated by morphine administrations in expression phase. These positive changes were significantly inhibited by microinjecting EX527 into the VLO. These results suggest that SIRT1 in the VLO may mediate morphine-induced behavioral sensitization and the overexpression of SIRT1, p-ERK and BDNF could be the potential mechanism. Taken together, the results of our research provide evidence to support that SIRT1 play an important role in morphine vulnerability and microinjecting EX527 into the VLO could significantly suppress morphine addiction in rats.

吗啡成瘾被归类为慢性反复发作的脑部疾病，通常会导致精神障碍，伴随疾病和早逝。最近的证据表明，Sirtuin 1（SIRT1）在学习，记忆和奖励中起着至关重要的作用，但是，其在吗啡成瘾中的作用仍不清楚。我们探讨了腹外侧眶皮质（VLO）中的SIRT1是否与吗啡成瘾及其潜在机制有关。我们应用吗啡诱导的行为致敏范例，研究了将SIRT1抑制剂EX527微注射到VLO中是否会影响大鼠的行为。此外，我们专注于细胞外信号调节蛋白激酶（ERK）和脑源性神经营养因子（BDNF）的表达，SIRT1的潜在下游目标。将EX527显微注射到VLO中可显着抑制吗啡诱导的行为敏化。我们发现，在表达阶段，吗啡给药显着上调了VLO中SIRT1，磷酸化ERK（p-ERK）和BDNF的表达。通过将EX527显微注射到VLO中，这些阳性变化被显着抑制。这些结果表明，VLO中的SIRT1可能介导吗啡诱导的行为敏化，SIRT1，p-ERK和BDNF的过度表达可能是其潜在机制。两者合计，我们的研究结果提供证据支持SIRT1在吗啡脆弱性中起重要作用，并且将EX527微量注射到VLO中可以显着抑制大鼠吗啡成瘾。表达期吗啡给药显着上调了VLO中的磷酸化ERK（p-ERK）和BDNF。通过将EX527显微注射到VLO中，这些阳性变化被显着抑制。这些结果表明，VLO中的SIRT1可能介导吗啡诱导的行为敏化，SIRT1，p-ERK和BDNF的过度表达可能是其潜在机制。两者合计，我们的研究结果提供证据支持SIRT1在吗啡脆弱性中起重要作用，并且将EX527微量注射到VLO中可以显着抑制大鼠吗啡成瘾。表达期吗啡给药显着上调了VLO中的磷酸化ERK（p-ERK）和BDNF。通过将EX527显微注射到VLO中，这些阳性变化被显着抑制。这些结果表明，VLO中的SIRT1可能介导吗啡诱导的行为敏化，SIRT1，p-ERK和BDNF的过度表达可能是其潜在机制。两者合计，我们的研究结果提供证据支持SIRT1在吗啡脆弱性中起重要作用，并且将EX527微量注射到VLO中可以显着抑制大鼠吗啡成瘾。这些结果表明，VLO中的SIRT1可能介导吗啡诱导的行为敏化，SIRT1，p-ERK和BDNF的过度表达可能是其潜在机制。两者合计，我们的研究结果提供证据支持SIRT1在吗啡脆弱性中起重要作用，并且将EX527微量注射到VLO中可以显着抑制大鼠吗啡成瘾。这些结果表明，VLO中的SIRT1可能介导吗啡诱导的行为敏化，SIRT1，p-ERK和BDNF的过度表达可能是其潜在机制。两者合计，我们的研究结果提供证据支持SIRT1在吗啡脆弱性中起重要作用，并且将EX527微量注射到VLO中可以显着抑制大鼠吗啡成瘾。