title: Expression levels of the BDNF gene and histone modifications around its promoters in the ventral tegmental area and locus ceruleus of rats during forced abstinence from morphine.
abstract: Brain-derived neurotrophic factor (BDNF) plays a role in mediating molecular, cellular, and behavioral adaptations underlying drug addiction. Here, we examined the influence of withdrawal from repeated morphine treatment on the expression of BDNF mRNA in the ventral tegmental area (VTA) and locus coeruleus (LC) of the rat brain. We also studied whether alternations in mRNA levels of BDNF in these tissues are associated with histone modifications around promoters II and III of the BDNF gene. Thus, chromatin immunoprecipitation (CHIP) and quantitative (q)-PCR were employed to assess acetylation of histone H3 at K9/K14 and trimethylation of histone H3 at K9. Results of qRT-PCR showed that levels of BDNF mRNA in both VTA and LC were significantly increased 7 days rather than 2 h or 24 h following the last injection of morphine. Consistently, CHIP and qPCR analysis revealed that on day 7 of morphine abstinence, both VTA and LC levels of histone methylation at BDNF promoters II and III of morphine treated rats were significantly lower than control animals. Morphine withdrawal caused only a significant increase in H3 acetylation at the promoter II in the LC. These data demonstrate the involvement of histone H3 methylation in the regulation of gene expression in the VTA and LC of rats during forced abstinence of morphine.
authors.affiliation: Department of Biochemistry, Shiraz University of Medical Sciences, P.O. Box 1167, Shiraz, Iran.
authors.forename: Farideh Jalali
authors.initials: FJ
authors.lastname: Mashayekhi
authors.forename: Mozhgan
authors.initials: M
authors.lastname: Rasti
authors.forename: Mostafa
authors.initials: M
authors.lastname: Rahvar
authors.forename: Pooneh
authors.initials: P
authors.lastname: Mokarram
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Namavar
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Owji
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D017931:DNA Primers; D006657:Histones / Q000378:metabolism*; D008125:Locus Coeruleus / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000008:administration & dosage* / Q000009:adverse effects; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013375:Substance Withdrawal Syndrome; D017557:Ventral Tegmental Area / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017931:DNA Primers; D006657:Histones; D009020:Morphine