Neuropharmacology

Biography

Biography: Jin-Song Bian

Abstract

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 μ-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 pre-treatment suppressed naloxone-stimulated activation of protein kinase C (PKC) α, 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.