PMID- 25072653
OWN - NLM
STAT- MEDLINE
DCOM- 20151109
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 7
DP  - 2014
TI  - Synapse density and dendritic complexity are reduced in the prefrontal cortex 
      following seven days of forced abstinence from cocaine self-administration.
PG  - e102524
LID - 10.1371/journal.pone.0102524 [doi]
LID - e102524
AB  - Chronic cocaine exposure in both human addicts and in rodent models of addiction 
      reduces prefrontal cortical activity, which subsequently dysregulates reward 
      processing and higher order executive function. The net effect of this impaired 
      gating of behavior is enhanced vulnerability to relapse. Previously we have shown 
      that cocaine-induced increases in brain-derived neurotrophic factor (BDNF) 
      expression in the medial prefrontal cortex (PFC) is a neuroadaptive mechanism 
      that blunts the reinforcing efficacy of cocaine. As BDNF is known to affect 
      neuronal survival and synaptic plasticity, we tested the hypothesis that 
      abstinence from cocaine self-administration would lead to alterations in neuronal 
      morphology and synaptic density in the PFC. Using a novel technique, array 
      tomography and Golgi staining, morphological changes in the rat PFC were analyzed 
      following 14 days of cocaine self-administration and 7 days of forced abstinence. 
      Our results indicate that overall dendritic branching and total synaptic density 
      are significantly reduced in the rat PFC. In contrast, the density of thin 
      dendritic spines are significantly increased on layer V pyramidal neurons of the 
      PFC. These findings indicate that dynamic structural changes occur during cocaine 
      abstinence that may contribute to the observed hypo-activity of the PFC in 
      cocaine-addicted individuals.
FAU - Rasakham, Khampaseuth
AU  - Rasakham K
AD  - MassGeneral Institute for Neurodegenerative Disease, Massachusetts General 
      Hospital, Boston, Massachusetts, United States of America.
FAU - Schmidt, Heath D
AU  - Schmidt HD
AD  - Center for Neurobiology and Behavior, Department of Psychiatry, Perelman School 
      of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United 
      States of America.
FAU - Kay, Kevin
AU  - Kay K
AD  - MassGeneral Institute for Neurodegenerative Disease, Massachusetts General 
      Hospital, Boston, Massachusetts, United States of America.
FAU - Huizenga, Megan N
AU  - Huizenga MN
AD  - MassGeneral Institute for Neurodegenerative Disease, Massachusetts General 
      Hospital, Boston, Massachusetts, United States of America.
FAU - Calcagno, Narghes
AU  - Calcagno N
AD  - MassGeneral Institute for Neurodegenerative Disease, Massachusetts General 
      Hospital, Boston, Massachusetts, United States of America.
FAU - Pierce, R Christopher
AU  - Pierce RC
AD  - Center for Neurobiology and Behavior, Department of Psychiatry, Perelman School 
      of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United 
      States of America.
FAU - Spires-Jones, Tara L
AU  - Spires-Jones TL
AD  - MassGeneral Institute for Neurodegenerative Disease, Massachusetts General 
      Hospital, Boston, Massachusetts, United States of America.
FAU - Sadri-Vakili, Ghazaleh
AU  - Sadri-Vakili G
AD  - MassGeneral Institute for Neurodegenerative Disease, Massachusetts General 
      Hospital, Boston, Massachusetts, United States of America.
LA  - eng
GR  - K01 DA18678/DA/NIDA NIH HHS/United States
GR  - R01 DA022339/DA/NIDA NIH HHS/United States
GR  - R01 DA033641/DA/NIDA NIH HHS/United States
GR  - DA033641/DA/NIDA NIH HHS/United States
GR  - K02 DA018678/DA/NIDA NIH HHS/United States
GR  - K01 DA030445/DA/NIDA NIH HHS/United States
GR  - DA22339/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140729
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cocaine/*administration & dosage
MH  - Cocaine-Related Disorders/*metabolism/*pathology
MH  - *Dendrites
MH  - Disease Models, Animal
MH  - Male
MH  - Prefrontal Cortex/*metabolism/*pathology
MH  - Rats
MH  - Synapses/*metabolism
MH  - Time Factors
PMC - PMC4114454
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/07/30 06:00
MHDA- 2015/11/10 06:00
PMCR- 2014/07/29
CRDT- 2014/07/30 06:00
PHST- 2014/02/26 00:00 [received]
PHST- 2014/06/19 00:00 [accepted]
PHST- 2014/07/30 06:00 [entrez]
PHST- 2014/07/30 06:00 [pubmed]
PHST- 2015/11/10 06:00 [medline]
PHST- 2014/07/29 00:00 [pmc-release]
AID - PONE-D-14-09025 [pii]
AID - 10.1371/journal.pone.0102524 [doi]
PST - epublish
SO  - PLoS One. 2014 Jul 29;9(7):e102524. doi: 10.1371/journal.pone.0102524. 
      eCollection 2014.