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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, RESULTS, METHODS. Meshes: Adenylyl Cyclases, Analgesics, Opioid, Animals, Behavior, Animal, Cell Line, Corpus Striatum, Cyclic AMP, Cyclic AMP Response Element-Binding Protein, Enkephalin, Ala(2)-MePhe(4)-Gly(5)-, Gene Expression Regulation, Humans, Hydrogen Sulfide, Male, Mice, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Morphine, Morphine Dependence, Naloxone, Phosphorylation, Signal Transduction.
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Does hydrogen sulfide attenuate opioid dependence by suppression of adenylate cyclase/cAMP pathway? Context: The best-established mechanism of opioid dependence is the up-regulation of adenylate cyclase (AC)/cAMP pathway, which was reported to be negatively regulated by hydrogen sulfide (H2S), a novel endogenous neuromodulator. The present study was, therefore, designed to determine whether H2S is able to attenuate the development of opioid dependence via down-regulating AC/cAMP pathway. We demonstrated that application of sodium hydrosulphide (NaHS) and GYY4137, two donors of H2S, significantly alleviated naloxone-induced robust withdrawal jumping (the most sensitive and reliable index of opioid physical dependence) in morphine-treated mice. Repeated treatment with NaHS inhibited the up-regulated protein expression of AC in the striatum of morphine-dependent mice. Furthermore, NaHS also attenuated morphine/naloxone-elevated mRNA levels of AC isoform 1 and 8, production of cAMP, and phosphorylation of cAMP response element-binding protein (CREB) in mice striatum. These effects were mimicked by the application of exogenous H2S or over-expression of cystathione-β-synthase, an H2S -producing enzyme, in SH-SY5Y neuronal cells on treatment with [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-Enkephalin, a selective μ-opioid receptor agonist. Blockade of extracellular-regulated protein kinase 1/2 (ERK1/2) with its specific inhibitor attenuated naloxone-induced CREB phosphorylation. Pretreatment with NaHS or stimulation of endogenous H2S production also significantly suppressed opioid withdrawal-induced ERK1/2 activation in mice striatum or SH-SY5Y cells. H2S treatment is important in prevention of the development of opioid dependence via suppression of cAMP pathway in both animal and cellular models.
assistant
Our data suggest a potential role of H2S in attenuating the development of opioid dependence, and the underlying mechanism is closely related to the inhibition of AC/cAMP pathway. Final Decision: yes