PMID- 22790874
OWN - NLM
STAT- MEDLINE
DCOM- 20130510
LR  - 20240318
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Print)
IS  - 0033-3158 (Linking)
VI  - 224
IP  - 4
DP  - 2012 Dec
TI  - Association of time-dependent changes in mu opioid receptor mRNA, but not BDNF, 
      TrkB, or MeCP2 mRNA and protein expression in the rat nucleus accumbens with 
      incubation of heroin craving.
PG  - 559-71
LID - 10.1007/s00213-012-2784-z [doi]
AB  - RATIONALE AND OBJECTIVES: Responding to heroin cues progressively increases after 
      cessation of heroin self-administration (incubation of heroin craving). We 
      investigated whether this incubation is associated with time-dependent changes in 
      brain-derived neurotrophic factor (BDNF) and methyl-CpG binding protein 2 (MeCP2) 
      signaling and mu opioid receptor (MOR) expression in nucleus accumbens (NAc), 
      dorsal striatum (DS), and medial prefrontal cortex (mPFC). We also investigated 
      the effect of the preferential MOR antagonist naloxone on cue-induced heroin 
      seeking during abstinence. METHODS: We trained rats to self-administer heroin or 
      saline for 9-10 days and then dissected the NAc, DS, and mPFC at different 
      abstinence days and measured mRNA and protein levels of BDNF, TrkB, and MeCP2, as 
      well as MOR mRNA (Oprm1). In other groups, we assessed cue-induced heroin seeking 
      in extinction tests after 1, 11, and 30 abstinence days, and naloxone's 
      (0-1.0 mg/kg) effect on extinction responding after 1 and 15 days. RESULTS: 
      Cue-induced heroin seeking progressively increased or incubated during 
      abstinence. This incubation was not associated with changes in BDNF, TrkB, or 
      MeCP2 mRNA or protein levels in NAc, DS, or mPFC; additionally, no molecular 
      changes were observed after extinction tests on day 11. In NAc, but not DS or 
      mPFC, MOR mRNA decreased on abstinence day 1 and returned to basal levels over 
      time. Naloxone significantly decreased cue-induced heroin seeking after 15 
      abstinence days but not 1 day. CONCLUSIONS: Results suggest a role of MOR in 
      incubation of heroin craving. As previous studies implicated NAc BDNF in 
      incubation of cocaine craving, our data suggest that different mechanisms 
      contribute to incubation of heroin versus cocaine craving.
FAU - Theberge, Florence R M
AU  - Theberge FR
AD  - Behavioral Neuroscience Branch, IRP/NIDA/NIH/DHHS, 251 Bayview Boulevard, 
      Baltimore, MD 21224, USA.
FAU - Pickens, Charles L
AU  - Pickens CL
FAU - Goldart, Evan
AU  - Goldart E
FAU - Fanous, Sanya
AU  - Fanous S
FAU - Hope, Bruce T
AU  - Hope BT
FAU - Liu, Qing-Rong
AU  - Liu QR
FAU - Shaham, Yavin
AU  - Shaham Y
LA  - eng
GR  - ZIA DA000434/ImNIH/Intramural NIH HHS/United States
GR  - ZIA DA000434-12/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20120712
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Mecp2 protein, rat)
RN  - 0 (Methyl-CpG-Binding Protein 2)
RN  - 0 (Narcotic Antagonists)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Opioid, mu)
RN  - 36B82AMQ7N (Naloxone)
RN  - 70D95007SX (Heroin)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor
MH  - Cues
MH  - Dose-Response Relationship, Drug
MH  - Gene Expression Regulation/*drug effects
MH  - Heroin/*administration & dosage
MH  - Heroin Dependence/psychology
MH  - Male
MH  - Methyl-CpG-Binding Protein 2/genetics
MH  - Naloxone/administration & dosage/*pharmacology
MH  - Narcotic Antagonists/administration & dosage/pharmacology
MH  - Nucleus Accumbens/drug effects/metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/genetics
MH  - Receptors, Opioid, mu/*genetics
MH  - Self Administration
MH  - Time Factors
PMC - PMC3593041
MID - NIHMS444482
COIS- The authors declare that they do not have any conflicts of interest (financial or 
      otherwise) related to the data presented in this manuscript.
EDAT- 2012/07/14 06:00
MHDA- 2013/05/11 06:00
PMCR- 2013/12/01
CRDT- 2012/07/14 06:00
PHST- 2012/02/08 00:00 [received]
PHST- 2012/06/15 00:00 [accepted]
PHST- 2012/07/14 06:00 [entrez]
PHST- 2012/07/14 06:00 [pubmed]
PHST- 2013/05/11 06:00 [medline]
PHST- 2013/12/01 00:00 [pmc-release]
AID - 10.1007/s00213-012-2784-z [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2012 Dec;224(4):559-71. doi: 
      10.1007/s00213-012-2784-z. Epub 2012 Jul 12.