Effect of Yulangsan Polysaccharide on the Reinstatement of Morphine-Induced Conditioned Place Preference in Sprague–Dawley Rats
We previously reported that Yulangsan polysaccharide (YLSP), which was isolated from the root of Millettia pulchra Kurz, attenuates withdrawal symptoms of morphine dependence by regulating the nitric oxide pathway and modulating monoaminergic neurotransmitters. In this study, we investigated the effects and mechanism of YLSP on the reinstatement of morphine-induced conditioned place preference (CPP) in rats. A CPP procedure was employed to assess the behavior of rats, and indicators of serum and four brain regions (nucleus accumbens, ventral tegmental area, hippocampus and prefrontal cortex) were determined to explore its underlying mechanism. YLSP inhibited priming morphine-induced reinstatement of CPP in a dose-dependent manner. YLSP markedly reduced nitric oxide and nitric oxide synthase levels in the brain. Moreover, YLSP significantly decreased the dopamine and norepinephrine levels in the serum and brain. Furthermore, YLSP significantly decreased cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) concentrations, inhibited the expression of dopamine D1 receptors and cAMP response element binding protein mRNA, and improved the expression of dopamine D2 receptor mRNA in the four brain regions. Our findings indicated that YLSP could inhibit the reinstatement of morphine-induced CPP possibly by modulating the NO-cGMP and D1R-cAMP signaling pathways.
KeywordsYulangsan polysaccharide Conditioned place preference Morphine Dopamine receptor CREB
Compliance with Ethical Standards
Conflict of interest
The authors declare that there are no conflicts of interest.
- 20.Kowalczyk WJ, Phillips KA, Jobes ML, Kennedy AP, Ghitza UE, Agage DA, Schmittner JP, Epstein DH, Preston KL (2015) Clonidine maintenance prolongs opioid abstinence and decouples stress from craving in daily life: a randomized controlled trial with ecological momentary assessment. Am J Psychiatry 172(8):760–767. https://doi.org/10.1176/appi.ajp.2014.14081014 CrossRefPubMedGoogle Scholar
- 21.George P, Charles W (1998) The rat brain in stereotaxic coordinates (Qingchuan Zhuge translate. People’s Medical Publishing House, Beijing, 2007), p 32Google Scholar
- 26.Chen C, Fan Q, Nong Z, Chen W, Li Y, Huang L, Feng D, Pan X, Lan S (2018) Hyperbaric oxygen attenuates withdrawal symptoms by regulating monoaminergic neurotransmitters and NO signaling pathway at nucleus accumbens in morphine-dependent rats. Neurochem Res. https://doi.org/10.1007/s11064-017-2447-x Google Scholar