PMID- 19345340
OWN - NLM
STAT- MEDLINE
DCOM- 20090902
LR  - 20220310
IS  - 1873-2402 (Electronic)
IS  - 0006-3223 (Print)
IS  - 0006-3223 (Linking)
VI  - 66
IP  - 2
DP  - 2009 Jul 15
TI  - Role of ventral tegmental area glial cell line-derived neurotrophic factor in 
      incubation of cocaine craving.
PG  - 137-45
LID - 10.1016/j.biopsych.2009.02.009 [doi]
AB  - BACKGROUND: Ventral tegmental area (VTA) brain-derived neurotrophic factor (BDNF) 
      contributes to time-dependent increases in cue-induced cocaine seeking after 
      withdrawal (incubation of cocaine craving). Here, we studied the role of glial 
      cell line-derived neurotrophic factor (GDNF) in incubation of cocaine craving 
      because, like BDNF, GDNF provides trophic support to midbrain dopamine neurons. 
      METHODS: We first trained rats to self-administer intravenous cocaine for 10 days 
      (6 hours/d, cocaine injections were paired with a tone-light cue). We then 
      manipulated VTA GDNF function and assessed cue-induced cocaine seeking in 
      extinction tests after withdrawal from cocaine. RESULTS: VTA injections of an 
      adeno-associated virus (AAV) vector containing rat GDNF cDNA (5 x 10(8) viral 
      genomes) on withdrawal Day 1 increased cue-induced cocaine seeking on withdrawal 
      days 11 and 31; this effect was not observed after VTA injections of an AAV viral 
      vector containing red fluorescent protein (RFP). Additionally, VTA, but not 
      substantial nigra (SN), GDNF injections (1.25 microg or 12.5 microg/side) 
      immediately after the last cocaine self-administration session increased 
      cue-induced drug seeking on withdrawal days 3 and 10; this effect was reversed by 
      VTA injections of U0126, which inhibits the activity of extracellular 
      signal-regulated kinases (ERK). Finally, interfering with VTA GDNF function by 
      chronic delivery of anti-GDNF monoclonal neutralizing antibodies via minipumps 
      (600 ng/side/d) during withdrawal Days 1-14 prevented the time-dependent 
      increases in cue-induced cocaine seeking on withdrawal days 11 and 31. 
      CONCLUSIONS: Our results indicate that during the first weeks of withdrawal from 
      cocaine self-administration, GDNF-dependent neuroadaptations in midbrain VTA 
      neurons play an important role in the development of incubation of cocaine 
      craving.
FAU - Lu, Lin
AU  - Lu L
AD  - National Institute on Drug Dependence, Peking University, Beijing, China. 
      linlu@bjmu.edu.cn
FAU - Wang, Xi
AU  - Wang X
FAU - Wu, Ping
AU  - Wu P
FAU - Xu, Chunmei
AU  - Xu C
FAU - Zhao, Mei
AU  - Zhao M
FAU - Morales, Marisela
AU  - Morales M
FAU - Harvey, Brandon K
AU  - Harvey BK
FAU - Hoffer, Barry J
AU  - Hoffer BJ
FAU - Shaham, Yavin
AU  - Shaham Y
LA  - eng
GR  - ZIA DA000434-11/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090405
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 0 (Antibodies, Blocking)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - Animals
MH  - Antibodies, Blocking/pharmacology
MH  - Cell Line
MH  - Cocaine/adverse effects
MH  - Cocaine-Related Disorders/*psychology
MH  - Cues
MH  - Dependovirus/genetics
MH  - Genetic Vectors
MH  - Glial Cell Line-Derived Neurotrophic Factor/antagonists & 
      inhibitors/genetics/*metabolism
MH  - Male
MH  - Neuroglia/metabolism/*physiology
MH  - Rats
MH  - Rats, Long-Evans
MH  - Rats, Sprague-Dawley
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Substance Withdrawal Syndrome/metabolism
MH  - Ventral Tegmental Area/*cytology/*physiology
PMC - PMC3150198
MID - NIHMS312604
COIS- The authors report no biomedical financial interests or potential conflicts of 
      interest.
EDAT- 2009/04/07 09:00
MHDA- 2009/09/03 06:00
PMCR- 2011/08/04
CRDT- 2009/04/07 09:00
PHST- 2009/02/17 00:00 [received]
PHST- 2009/02/19 00:00 [accepted]
PHST- 2009/04/07 09:00 [entrez]
PHST- 2009/04/07 09:00 [pubmed]
PHST- 2009/09/03 06:00 [medline]
PHST- 2011/08/04 00:00 [pmc-release]
AID - S0006-3223(09)00221-2 [pii]
AID - 10.1016/j.biopsych.2009.02.009 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2009 Jul 15;66(2):137-45. doi: 10.1016/j.biopsych.2009.02.009. 
      Epub 2009 Apr 5.