• Neuroscience · Dec 2013

    Opiate exposure and withdrawal dynamically regulate mRNA expression in the serotonergic dorsal raphe nucleus.

    • J W Lunden and L G Kirby.
    • Department of Anatomy and Cell Biology, Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, USA.
    • Neuroscience. 2013 Dec 19;254:160-72.

    AbstractPrevious results from our lab suggest that hypofunctioning of the serotonergic (5-HT) dorsal raphe nucleus (DRN) is involved in stress-induced opiate reinstatement. To further investigate the effects of morphine dependence and withdrawal on the 5-HT DRN system, we measured gene expression at the level of mRNA in the DRN during a model of morphine dependence, withdrawal and post withdrawal stress exposure in rats. Morphine pellets were implanted for 72h and then either removed or animals were injected with naloxone to produce spontaneous or precipitated withdrawal, respectively. Animals exposed to these conditions exhibited withdrawal symptoms including weight loss, wet dog shakes and jumping behavior. Gene expression for brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), corticotrophin releasing-factor (CRF)-R1, CRF-R2, alpha 1 subunit of the GABAA receptor (GABAA-α1), μ-opioid receptor (MOR), 5-HT1A receptor, tryptophan hydroxylase2 (TPH2) and the 5-HT transporter was then measured using quantitative real-time polymerase chain reaction at multiple time-points across the model of morphine exposure, withdrawal and post withdrawal stress. Expression levels of BDNF, TrkB and CRF-R1 mRNA were decreased during both morphine exposure and following 7days of withdrawal. CRF-R2 mRNA expression was elevated after 7days of withdrawal. 5-HT1A receptor mRNA expression was decreased following 3h of morphine exposure, while TPH2 mRNA expression was decreased after 7days of withdrawal with swim stress. There were no changes in the expression of GABAA-α1, MOR or 5-HT transporter mRNA. Collectively these results suggest that alterations in neurotrophin support, CRF-dependent stress signaling, 5-HT synthesis and release may underlie 5-HT DRN hypofunction that can potentially lead to stress-induced opiate relapse.Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

      Pubmed     Full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…