PMID- 23682998
OWN - NLM
STAT- MEDLINE
DCOM- 20140127
LR  - 20211021
IS  - 1601-183X (Electronic)
IS  - 1601-1848 (Print)
IS  - 1601-183X (Linking)
VI  - 12
IP  - 5
DP  - 2013 Jul
TI  - Cortical-striatal gene expression in neonatal hippocampal lesion (NVHL)-amplified 
      cocaine sensitization.
PG  - 564-75
LID - 10.1111/gbb.12051 [doi]
AB  - Cortical-striatal circuit dysfunction in mental illness may enhance addiction 
      vulnerability. Neonatal ventral hippocampal lesions (NVHL) model this dual 
      diagnosis causality by producing a schizophrenia syndrome with enhanced 
      responsiveness to addictive drugs. Rat genome-wide microarrays containing >24 000 
      probesets were used to examine separate and co-occurring effects of NVHLs and 
      cocaine sensitization (15 mg/kg/day x 5 days) on gene expression within medial 
      prefrontal cortex (MPFC), nucleus accumbens (NAC), and caudate-putamen (CAPU). 
      Two weeks after NVHLs robustly amplified cocaine behavioral sensitization, brains 
      were harvested for genes of interest defined as those altered at P < 0.001 by 
      NVHL or cocaine effects or interactions. Among 135 genes so impacted, NVHLs 
      altered twofold more than cocaine, with half of all changes in the NAC. Although 
      no genes were changed in the same direction by both NVHL and cocaine history, the 
      anatomy and directionality of significant changes suggested synergy on the neural 
      circuit level generative of compounded behavioral phenotypes: NVHL predominantly 
      downregulated expression in MPFC and NAC while NVHL and cocaine history mostly 
      upregulated CAPU expression. From 75 named genes altered by NVHL or cocaine, 27 
      had expression levels that correlated significantly with degree of behavioral 
      sensitization, including 11 downregulated by NVHL in MPFC/NAC, and 10 upregulated 
      by NVHL or cocaine in CAPU. These findings suggest that structural and functional 
      impoverishment of prefrontal-cortical-accumbens circuits in mental illness is 
      associated with abnormal striatal plasticity compounding with that in addictive 
      disease. Polygenetic interactions impacting neuronal signaling and morphology 
      within these networks likely contribute to addiction vulnerability in mental 
      illness.
CI  - (c) 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics 
      Society.
FAU - Chambers, R A
AU  - Chambers RA
AD  - Lab for Translational Neuroscience of Dual Diagnosis & Development, Department of 
      Psychiatry, Institute for Psychiatric Research, Indiana University School of 
      Medicine, Indianapolis, IN 46202, USA. robchamb@iupui.edu
FAU - McClintick, J N
AU  - McClintick JN
FAU - Sentir, A M
AU  - Sentir AM
FAU - Berg, S A
AU  - Berg SA
FAU - Runyan, M
AU  - Runyan M
FAU - Choi, K H
AU  - Choi KH
FAU - Edenberg, H J
AU  - Edenberg HJ
LA  - eng
GR  - K08 DA019850/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130622
PL  - England
TA  - Genes Brain Behav
JT  - Genes, brain, and behavior
JID - 101129617
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - Animals
MH  - Cocaine/*pharmacology
MH  - Cocaine-Related Disorders/genetics/*metabolism
MH  - Gene Expression Profiling
MH  - Hippocampus/pathology
MH  - Male
MH  - Nucleus Accumbens/drug effects/*metabolism
MH  - Prefrontal Cortex/drug effects/*metabolism
MH  - Putamen/drug effects/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Transcription, Genetic
PMC - PMC4170677
MID - NIHMS626274
COIS- The Authors have no conflicts of interest to report.
EDAT- 2013/05/21 06:00
MHDA- 2014/01/28 06:00
PMCR- 2014/09/22
CRDT- 2013/05/21 06:00
PHST- 2013/01/07 00:00 [received]
PHST- 2013/05/01 00:00 [revised]
PHST- 2013/05/14 00:00 [accepted]
PHST- 2013/05/21 06:00 [entrez]
PHST- 2013/05/21 06:00 [pubmed]
PHST- 2014/01/28 06:00 [medline]
PHST- 2014/09/22 00:00 [pmc-release]
AID - 10.1111/gbb.12051 [doi]
PST - ppublish
SO  - Genes Brain Behav. 2013 Jul;12(5):564-75. doi: 10.1111/gbb.12051. Epub 2013 Jun 
      22.