Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440033, Maharashtra, India.
Neuropeptides. 2012 Oct;46(5):217-21. doi: 10.1016/j.npep.2012.06.002. Epub 2012 Aug 3.
Recent studies have provided convincing evidences for co-morbidity between opioid addiction and obsessive-compulsive disorder (OCD), and the involvement of the corticotrophin-releasing factor (CRF) in the effects of morphine-withdrawal. Some scanty evidences also point towards the role of CRF in OCD and related disorders. But, no evidence indicated the role of CRF in morphine withdrawal associated obsessive-compulsive behavior (OCB). Therefore, the present study investigated the role of CRF in morphine-withdrawal induced OCB in mice. Marble-burying behavior in mice was used to assess OCB as this model has good predictive and face validity. The results revealed that acute morphine dose dependently attenuated the marble burying behavior, whereas withdrawal of chronic morphine was associated with significant rise in marble burying behavior. This indicates the differential effect of acute morphine and chronic morphine-withdrawal on OCB. Further, acute treatment with CRF receptor antagonists like antalarmin (2 and 4 μg/mouse, i.c.v.) or astressin-2B (3 and 10 nmol/mouse, i.c.v.) dose dependently attenuated the peak morphine-withdrawal induced increase in marble burying behavior. Moreover, concomitant treatment with antalarmin (4 μg/mouse, i.c.v.) or astressin-2B (10 nmol/mouse, i.c.v.) along with morphine blocked the morphine-withdrawal associated exacerbation of OCB. These results indicate that OCB associated with morphine withdrawal state is partly mediated by the activation of central CRF receptors.
最近的研究为阿片类药物成瘾和强迫症（OCD）之间的共病提供了令人信服的证据，以及促肾上腺皮质释放因子（CRF）在吗啡戒断效应中的作用。一些有限的证据也表明 CRF 在 OCD 和相关疾病中的作用。但是，没有证据表明 CRF 在与吗啡戒断相关的强迫行为（OCB）中起作用。因此，本研究调查了 CRF 在吗啡戒断引起的小鼠 OCB 中的作用。使用小鼠埋珠行为来评估 OCB，因为这种模型具有良好的预测性和有效性。结果表明，急性吗啡剂量依赖性地减弱了埋珠行为，而慢性吗啡戒断与埋珠行为显著增加有关。这表明急性吗啡和慢性吗啡戒断对 OCB 的不同影响。此外，CRF 受体拮抗剂如 antalarmin（2 和 4 μg/只，脑室内注射）或 astressin-2B（3 和 10 nmol/只，脑室内注射）的急性治疗剂量依赖性地减弱了吗啡戒断引起的埋珠行为的峰值增加。此外，同时给予 antalarmin（4 μg/只，脑室内注射）或 astressin-2B（10 nmol/只，脑室内注射）与吗啡一起阻断了与吗啡戒断相关的 OCB 恶化。这些结果表明，与吗啡戒断状态相关的 OCB 部分是由中枢 CRF 受体的激活介导的。
