PMID- 24055683
OWN - NLM
STAT- MEDLINE
DCOM- 20150223
LR  - 20211021
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 254
DP  - 2013 Dec 19
TI  - Opiate exposure and withdrawal dynamically regulate mRNA expression in the 
      serotonergic dorsal raphe nucleus.
PG  - 160-72
LID - S0306-4522(13)00787-2 [pii]
LID - 10.1016/j.neuroscience.2013.08.071 [doi]
AB  - Previous 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-alpha1), mu-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-alpha1, 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.
CI  - Copyright (c) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Lunden, J W
AU  - Lunden JW
AD  - Department of Anatomy and Cell Biology, Center for Substance Abuse Research, 
      Temple University School of Medicine, Philadelphia, PA 19140, USA.
FAU - Kirby, L G
AU  - Kirby LG
LA  - eng
GR  - P30 DA013429/DA/NIDA NIH HHS/United States
GR  - R01 DA020126/DA/NIDA NIH HHS/United States
GR  - R01DA020126/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130920
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (RNA, Messenger)
RN  - 76I7G6D29C (Morphine)
SB  - IM
MH  - Animals
MH  - Gene Expression Regulation/drug effects
MH  - Male
MH  - Morphine/*administration & dosage
MH  - Opioid-Related Disorders/genetics/*metabolism
MH  - RNA, Messenger/*biosynthesis/drug effects/genetics
MH  - Raphe Nuclei/drug effects/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonergic Neurons/drug effects/*metabolism
MH  - Substance Withdrawal Syndrome/genetics/*metabolism
PMC - PMC3856937
MID - NIHMS532263
OTO - NOTNLM
OT  - 5-HT
OT  - BDNF
OT  - CPP
OT  - CRF
OT  - DRN
OT  - FS
OT  - GABA(A)-alpha1
OT  - MOR
OT  - PCR
OT  - SERT
OT  - TPH2
OT  - TrkB
OT  - VTA
OT  - alpha 1 subunit of the GABA(A) receptor
OT  - brain-derived neurotrophic factor
OT  - conditioned place-preference
OT  - corticotrophin-releasing factor
OT  - dorsal raphe nucleus
OT  - forced swim
OT  - gene expression
OT  - mRNA
OT  - morphine
OT  - polymerase chain reaction
OT  - serotonin
OT  - serotonin transporter
OT  - stress
OT  - tryptophan hydroxylase2
OT  - tyrosine kinase receptor B
OT  - ventral tegmental area
OT  - mu-opioid receptor
EDAT- 2013/09/24 06:00
MHDA- 2015/02/24 06:00
PMCR- 2014/12/19
CRDT- 2013/09/24 06:00
PHST- 2013/06/04 00:00 [received]
PHST- 2013/08/22 00:00 [revised]
PHST- 2013/08/31 00:00 [accepted]
PHST- 2013/09/24 06:00 [entrez]
PHST- 2013/09/24 06:00 [pubmed]
PHST- 2015/02/24 06:00 [medline]
PHST- 2014/12/19 00:00 [pmc-release]
AID - S0306-4522(13)00787-2 [pii]
AID - 10.1016/j.neuroscience.2013.08.071 [doi]
PST - ppublish
SO  - Neuroscience. 2013 Dec 19;254:160-72. doi: 10.1016/j.neuroscience.2013.08.071. 
      Epub 2013 Sep 20.