Jin-Song Bian
National University of Singapore, Singapore
Scientific Tracks Abstracts: Neurochem Neuropharm
Addiction to opioid drugs is a serious clinical and social problem. Withdrawal-induced symptoms are the main cause of keeping drug-dependent individuals craving for continued opioids. Hydrogen sulfide (H2S) is a novel endogenous neuromodulator. The role of H2S in opioid induced syndrome was investigated in the present study. We found that exogenous application of NaHS, an H2S donor, significantly alleviated naloxone-precipitation induced robust withdrawal jumping in mice. Application of NaHS or stimulation of endogenous H2S production suppressed naloxone precipitation induced cAMP rebound and CREB phosphorylation. Our data suggest that H2S may produce beneficial effects against opioid addiction by suppression of AC/cAMP /CREB pathway. Hyperalgesia often occurs in opioid-induced withdrawal syndrome. In the present study, we also studied the effect of H2S on opioid withdrawal induced hyperalgesia. We found that application of NaHS together with three hourly injections of DAMGO (a �¼-opioid receptor agonist) attenuated naloxoneprecipitated withdrawal hyperalgesia. RT-PCR and Western blot analysis showed that NaHS significantly reversed the gene and protein expression of up-regulated spinal calcitonin gene-related peptide (CGRP) in naloxone-treated animals. NaHS also inhibited naloxone-induced cAMP rebound and cAMP response element-binding protein (CREB) phosphorylation in rat spinal cord. In addition, NaHS pretreatment suppressed naloxone-stimulated activation of protein kinase C (PKC) �±, Raf-1, and extracellular signal-regulated kinase (ERK) 1/2 in rat spinal cord. In conclusion, our data suggest that H2S prevents the development of opioid withdrawal induced symptoms via suppression of synthesis of CGRP through inhibition of AC/cAMP and PKC/Raf-1/ERK pathways.
Jin-Song Bian is an Associate Professor in Department of Pharmacology, Yong Loo Ling School of Medicine, National University of Singapore, Singapore. He earned his PhD degree from the University of Hong Kong. At Albert Einstein College of Medicine in USA, he completed his Post-doctoral training with an American Heart Association fellowship in 2003. His main research interest is biology of endogenous mediators (e.g. hydrogen sulfide). He has published over 80 papers in international journals including Cir Res, ARS, JASN.
Email: jinsong_bian@nuhs.edu.sg
