Thalidomide attenuates development of morphine dependence in mice by inhibiting PI3K/Akt and nitric oxide signaling pathways

Publication date: 2 March 2018 Source:Progress in Neuro-Psychopharmacology and Biological Psychiatry, Volume 82 Author(s): Muhammad Imran Khan, Majid Momeny, Sattar Ostadhadi, Samane Jahanabadi, Shahram Ejtemaei-Mehr, Bilqees Sameem, Ghazaleh Zarrinrad, Ahmad Reza Dehpour Morphine dependence and the subsequent withdrawal syndrome restrict its clinical use in management of chronic pain. The precise mechanism for the development of dependence is still elusive. Thalidomide is a glutamic acid derivative, recently has been reconsidered for its clinical use due to elucidation of different clinical effects. Phosphoinositide 3-kinase (PI3K) is an intracellular transducer enzyme which activates Akt which in turns increases the level of nitric oxide. It is well established that elevated levels of nitric oxide has a pivotal role in the development of morphine dependence. In the present study, we aimed to explore the effect of thalidomide on the development of morphine dependence targeting PI3K/Akt (PKB) and nitric oxide (NO) pathways. Male NMRI mice and human glioblastoma T98G cell line were used to study the effect of thalidomide on morphine dependence. In both models the consequent effect of thalidomide on PI3K/Akt and/or NO signaling in morphine dependence was determined. Thalidomide alone or in combination with PI3K inhibitor, Akt inhibitor or nitric oxide synthase (NOS) inhibitors significantly reduced naloxone induced withdrawal signs in morphine dependent mice. Also, th...
Source: Progress in Neuro Psychopharmacology and Biological Psychiatry - Category: Psychiatry Source Type: research