PMID- 26346883
OWN - NLM
STAT- MEDLINE
DCOM- 20170322
LR  - 20181113
IS  - 1573-6830 (Electronic)
IS  - 0272-4340 (Linking)
VI  - 36
IP  - 6
DP  - 2016 Aug
TI  - Expression of BDNF and TrkB Phosphorylation in the Rat Frontal Cortex During 
      Morphine Withdrawal are NO Dependent.
PG  - 839-849
LID - 10.1007/s10571-015-0267-6 [doi]
AB  - Nitric oxide (NO) mediates pharmacological effects of opiates including 
      dependence and abstinence. Modulation of NO synthesis during the induction phase 
      of morphine dependence affects manifestations of morphine withdrawal syndrome, 
      though little is known about mechanisms underlying this phenomenon. Neurotrophic 
      and growth factors are involved in neuronal adaptation during opiate dependence. 
      NO-dependent modulation of morphine dependence may be mediated by changes in 
      expression and activity of neurotrophic and/or growth factors in the brain. Here, 
      we studied the effects of NO synthesis inhibition during the induction phase of 
      morphine dependence on the expression of brain-derived neurotrophic factor 
      (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and 
      insulin-like growth factor 1 (IGF1) as well as their receptors in rat brain 
      regions after spontaneous morphine withdrawal in dependent animals. Morphine 
      dependence in rats was induced within 6 days by 12 injections of morphine in 
      increasing doses (10-100 mg/kg), and NO synthase inhibitor L-N(G)-nitroarginine 
      methyl ester (L-NAME) (10 mg/kg) was given 1 h before each morphine injection. 
      The expression of the BDNF, GDNF, NGF, IGF1, and their receptors in the frontal 
      cortex, striatum, hippocampus, and midbrain was assessed 40 h after morphine 
      withdrawal. L-NAME treatment during morphine intoxication resulted in an 
      aggravation of the spontaneous morphine withdrawal severity. Morphine withdrawal 
      was accompanied by upregulation of BDNF, IGF1, and their receptors TrkB and 
      IGF1R, respectively, on the mRNA level in the frontal cortex, and only BDNF in 
      hippocampus and midbrain. L-NAME administration during morphine intoxication 
      decreased abstinence-induced upregulation of these mRNAs in the frontal cortex, 
      hippocampus and midbrain. L-NAME prevented from abstinence-induced elevation of 
      mature but not pro-form of BDNF polypeptide in the frontal cortex. While morphine 
      abstinence did not affect TrkB protein levels as well as its phosphorylation 
      status, inhibition of NO synthesis decreased levels of phosphorylated TrkB after 
      withdrawal. Thus, NO signaling during induction of dependence may be involved in 
      the mechanisms of BDNF expression and processing at abstinence, thereby affecting 
      signaling through TrkB in the frontal cortex.
FAU - Peregud, Danil I
AU  - Peregud DI
AD  - Federal State Budgetary Institution "V. Serbsky Federal Medical Research Centre 
      for Psychiatry and Drug Addiction", of the Ministry of Health of the Russian 
      Federation, Moscow, Russia, 119002.
AD  - Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of 
      Sciences, 5a Butlerov Str., Moscow, Russia, 117485.
FAU - Yakovlev, Alexander A
AU  - Yakovlev AA
AD  - Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of 
      Sciences, 5a Butlerov Str., Moscow, Russia, 117485.
FAU - Stepanichev, Mikhail Yu
AU  - Stepanichev MY
AD  - Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of 
      Sciences, 5a Butlerov Str., Moscow, Russia, 117485.
FAU - Onufriev, Mikhail V
AU  - Onufriev MV
AD  - Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of 
      Sciences, 5a Butlerov Str., Moscow, Russia, 117485.
FAU - Panchenko, Leonid F
AU  - Panchenko LF
AD  - Federal State Budgetary Institution "V. Serbsky Federal Medical Research Centre 
      for Psychiatry and Drug Addiction", of the Ministry of Health of the Russian 
      Federation, Moscow, Russia, 119002.
AD  - Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, 
      Moscow, Russia, 125315.
FAU - Gulyaeva, Natalia V
AU  - Gulyaeva NV
AD  - Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of 
      Sciences, 5a Butlerov Str., Moscow, Russia, 117485. nata_gul@yahoo.com.
LA  - eng
PT  - Journal Article
DEP - 20150907
PL  - United States
TA  - Cell Mol Neurobiol
JT  - Cellular and molecular neurobiology
JID - 8200709
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 76I7G6D29C (Morphine)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Frontal Lobe/*drug effects/*metabolism
MH  - Hippocampus/drug effects/metabolism
MH  - Male
MH  - Morphine/administration & dosage/*pharmacology
MH  - Morphine Dependence/metabolism
MH  - Nitric Oxide/*metabolism
MH  - Phosphorylation
MH  - RNA, Messenger/metabolism
MH  - Rats, Wistar
MH  - Receptor, trkB/*metabolism
OTO - NOTNLM
OT  - BDNF
OT  - Morphine dependence
OT  - Nitric oxide
OT  - Rat brain
EDAT- 2015/09/09 06:00
MHDA- 2017/03/23 06:00
CRDT- 2015/09/09 06:00
PHST- 2015/07/13 00:00 [received]
PHST- 2015/08/29 00:00 [accepted]
PHST- 2015/09/09 06:00 [entrez]
PHST- 2015/09/09 06:00 [pubmed]
PHST- 2017/03/23 06:00 [medline]
AID - 10.1007/s10571-015-0267-6 [pii]
AID - 10.1007/s10571-015-0267-6 [doi]
PST - ppublish
SO  - Cell Mol Neurobiol. 2016 Aug;36(6):839-849. doi: 10.1007/s10571-015-0267-6. Epub 
      2015 Sep 7.