Background and Objective: The interface of the mesocorticolimbic dopamine system with other structures such as the hypothalamus is critical to long lasting molecular changes driving addiction. Increasing evidence has supported a contribution of the nuclear transcription factors in the development of addiction. We aim to examine the gene expression of NFκB, CREB and AP1in the hypothalamus of morphine-tolerant rats. Materials and Methods: Male Wistar rats were used and randomly allocated to either saline-treated or morphine-treated groups. The experimental groups received a regimen of 8 days treatments of saline (1 ml/kg) or morphine (10 mg/kg) twice daily. Induction of analgesic tolerance to repeated injections of morphine was assessed with a hotplate test of analgesia on day 8 of the schedule. On day 8, each rat was deeply anesthetized, decapitated and the hypothalamus was dissected immediately. The gene expression of NFκB, CREB and AP1 was examined by using a real-time PCR method. Results: The results of the hotplate test of analgesia revealed that morphine treatments for 8 days induced tolerance to the analgesic effect of the opioid. The qPCR results indicated that the gene expressions of the CREB and AP1 in the hypothalamus of the morphine tolerant group were significantly increased compared to the saline-treated group but the gene expression of NFκB was decreased. Conclusion: We conclude that the increases in the expression of CREB and AP1 as well as the decrease in NFκB involved, at least partly, in the development of molecular changes underlying morphine addiction and tolerance in the hypothalamus.
