Effect of Sirtuin-1 on Synaptic Plasticity in Nucleus Accumbens in a Rat Model of Heroin Addiction.

Content Provider	Europe PMC
Author	Xia, Baijuan Li, Yixin Li, Rongrong Yin, Dan Chen, Xingqiang Li, Jie Liang, Wenmei
Copyright Year	2018
Abstract	BackgroundSynaptic plasticity plays an important role in the process of addiction. This study investigated the relationship between synaptic plasticity and changes in addictive behavior and examined the expression of synaptic plasticity-associated proteins and genes in the nucleus accumbens (NAc) region in different rat models.Material/MethodsHeroin addiction, SIRT1-overexpression, and SIRT1-silenced rat models were established. Polymerase chain reaction gene chip technology, immunohistochemistry, Western blotting, and transmission electron microscopy were used to detect changes in synaptic plasticity-related gene and protein expression, and changes in the ultrastructure of synapses, in the NAc.ResultsNaloxone withdrawal symptoms appeared in the SIRT1-overexpression group. In the SIRT1-silenced group the symptoms were reduced. Immunohistochemistry and Western blotting results showed that FOXO1 expression decreased in the heroin addiction (HA) group but increased in the SIRT1-silenced group (p<0.05). The expression of Cdk5, Nf-κB, PSD95, and Syn was enhanced in the HA group (p<0.05) and further increased in the SIRT1-overexpression group but were reduced in the SIRT1-silenced group (p<0.05). The number of synapses increased in the HA group (p<0.05) along with mitochondrial swelling in the presynaptic membrane and obscuring of the synaptic cleft.ConclusionsSIRT1 and other synaptic plasticity-related genes in NAc are involved in the regulation of heroin addiction. SIRT1 overexpression can increase behavioral sensitization in the NAc of rats, and SIRT1 silencing might ease withdrawal symptoms and reduce conditioned place preferences.
ISSN	12341010
Journal	Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
Volume Number	24
PubMed Central reference number	PMC6016439
PubMed reference number	29870523
e-ISSN	16433750
DOI	10.12659/msm.910550
Language	English
Publisher	International Scientific Literature, Inc.
Publisher Date	2018-06-05
Access Restriction	Open
Rights License	This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) © Med Sci Monit, 2018
Subject Keyword	Heroin Neuronal Plasticity Nucleus Accumbens
Content Type	Text
Resource Type	Article
Subject	Medicine