Role of Dorsal Striatum Histone Deacetylase 5 in Incubation of Methamphetamine Craving
| Autor: | Eric J. Nestler, Xuan Li, Jennifer M. Bossert, Jian-Jun Zhang, Christopher W. Cowan, Kailyn F. R. Witonsky, Tamara Zeric, Maria B. Carreria, Christopher T. Richie, Olivia M. Lofaro, Yavin Shaham, Brandon K. Harvey, Hyeon Son, Felicia Surjono |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Drug-Seeking Behavior Craving Self Administration Striatum Biology Histone Deacetylases Methamphetamine Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Animals Incubation Biological Psychiatry Gene knockdown Histone deacetylase 5 Meth HDAC4 Corpus Striatum Rats Substance Withdrawal Syndrome 030104 developmental biology Endocrinology chemistry Gene Knockdown Techniques Central Nervous System Stimulants medicine.symptom 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Biological psychiatry. 84(3) |
| ISSN: | 1873-2402 |
| Popis: | Background Methamphetamine (meth) seeking progressively increases after withdrawal (incubation of meth craving). We previously demonstrated an association between histone deacetylase 5 (HDAC5) gene expression in the rat dorsal striatum and incubation of meth craving. Here we used viral constructs to study the causal role of dorsal striatum HDAC5 in this incubation. Methods In experiment 1 (overexpression), we injected an adeno-associated virus bilaterally into dorsal striatum to express either green fluorescent protein (control) or a mutant form of HDAC5, which strongly localized to the nucleus. After training rats to self-administer meth (10 days, 9 hours/day), we tested the rats for relapse to meth seeking on withdrawal days 2 and 30. In experiment 2 (knockdown), we injected an adeno-associated virus bilaterally into the dorsal striatum to express a short hairpin RNA either against luciferase (control) or against HDAC5. After training rats to self-administer meth, we tested the rats for relapse on withdrawal days 2 and 30. We also measured gene expression of other HDACs and potential HDAC5 downstream targets. Results We found that HDAC5 overexpression in dorsal striatum increased meth seeking on withdrawal day 30 but not day 2. In contrast, HDAC5 knockdown in the dorsal striatum decreased meth seeking on withdrawal day 30 but not on day 2; this manipulation also altered other HDACs (Hdac1 and Hdac4) and potential HDAC5 targets (Gnb4 and Suv39h1). Conclusions Results demonstrate a novel role of dorsal striatum HDAC5 in incubation of meth craving. These findings also set up future work to identify HDAC5 targets that mediate this incubation. |
| Databáze: | OpenAIRE |
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