Exogenous sodium hydrosulfide can attenuate naloxone-precipitated withdrawal syndromes and affect cAMP signaling pathway in heroin-dependent rat's nucleus accumbens.

BACKGROUND: H₂S is a novel type of endogenous neural regulatory factor and gaseous mediator. Exogenous H₂S can increase heroin-induced learning and memory damage in rat and alleviates heroin-induced rat hippocampus damage through antioxidant and anti-apoptosis effects. OBJECTIVE: Aim of this study was to identify whether hydrogen sulfide (H₂S) protects heroin withdrawal rat is related with adenylate cyclase (AC)-cAMP-protein kinase A (PKA)-cAMP response element-binding protein (CREB) signaling pathway in heroin-dependent rat's nucleus accumbens or not. METHODS: Male Spragne-Dawley rats were randomly divided into Saline + Saline group, Saline + sodium hydrosulfide (NaHS) group, Saline + Heroin group, NaHS + Heroin group according to the principle of increasing heroin dosage day by day, with the establishment of heroin-naloxone-induced withdrawal symptoms determined at day 10. Then the levels of H₂S and cAMP and AC and PKA activities were assayed, and the level of phosphorylated CREB (p-CREB), the levels of phosphorylated N-methyl-Daspartate receptor 1 subunit (p-NR1), phosphorylated N-methyl-D-aspartate receptor 2a subunit (p-NR2A) and phosphorylated N-methyl-Daspartate receptor 2b subunit (p-NR2B) were assayed in nucleus accumbens. RESULTS: Exogenous H₂S can alleviate heroin withdrawal symptoms by increasing the level of H2S level in nucleus accumbens. Exogenous H₂S can decrease the high activities of AC, PKA and the high levels of cAMP, p-CREB caused by heroin. Furthermore, exogenous H₂S can decrease the high level of p-NR1 and can increase the low levels of p-NR2A and p-NR2B caused by heroin. It is surprising that exogenous H₂S treatment alone was able to raise the activities of AC and PKA as well as the levels of cAMP, p-CREB, p-NR1, p-NR2A and p-NR2B. CONCLUSIONS: Exogenous H₂S decreases naloxone-precipitated withdrawal signs, maybe through decreasing AC/cAMP/PKA/CREB/NMDR signaling pathway in heroin-dependent rats' nucleus accumbens. [ABSTRACT FROM AUTHOR]