PMID- 18083141
OWN - NLM
STAT- MEDLINE
DCOM- 20080414
LR  - 20211020
IS  - 1873-2402 (Electronic)
IS  - 0006-3223 (Print)
IS  - 0006-3223 (Linking)
VI  - 63
IP  - 8
DP  - 2008 Apr 15
TI  - Strain differences in the gating-disruptive effects of apomorphine: relationship 
      to gene expression in nucleus accumbens signaling pathways.
PG  - 748-58
AB  - BACKGROUND: Prepulse inhibition (PPI) of startle is a measure of sensorimotor 
      gating that is deficient in certain psychiatric disorders, including 
      schizophrenia. Sprague Dawley (SD) rats are more sensitive to PPI-disruptive 
      effects of apomorphine (APO) at long interstimulus intervals (ISIs) (60-120 msec) 
      and less sensitive to PPI-enhancing effects of APO at short ISIs (10-30 msec) 
      compared with Long Evans (LE) rats. METHODS: Prepulse inhibition was tested in SD 
      and LE rats after APO (.5 mg/kg) or vehicle in a within- subject design and 
      sacrificed 14 days later. Total RNA was extracted from the nucleus accumbens 
      (NAC). Approximately 700 dopamine-relevant transcripts on the Affymetrix 230 2.0 
      microarray were analyzed. RESULTS: As previously reported, SD rats exhibited 
      greater APO-induced PPI deficits at long intervals and less APO-induced PPI 
      enhancement at short intervals compared with LE rats. One hundred four genes 
      exhibited significantly different NAC expression levels in these two strains. 
      Pathway analysis revealed that many of these genes contribute to dopamine 
      receptor signaling, synaptic long-term potentiation, or inositol phosphate 
      metabolism. The expression of some genes significantly correlated with measures 
      of APO-induced PPI sensitivity in either SD or LE rats. The expression of select 
      genes was validated by real-time reverse transcription polymerase chain reaction 
      (RT-PCR). CONCLUSIONS: Differences in PPI APO sensitivity in SD versus LE rats 
      are robust and reproducible and may be related to strain differences in the 
      expression of genes that regulate signal transduction in the NAC. These genes 
      could facilitate the identification of targets for ameliorating heritable gating 
      deficits in brain disorders such as schizophrenia.
FAU - Shilling, Paul D
AU  - Shilling PD
AD  - Department of Psychiatry, University of California, San Diego, La Jolla, 
      California 92093, USA.
FAU - Saint Marie, Richard L
AU  - Saint Marie RL
FAU - Shoemaker, Jody M
AU  - Shoemaker JM
FAU - Swerdlow, Neal R
AU  - Swerdlow NR
LA  - eng
GR  - R01 MH053484/MH/NIMH NIH HHS/United States
GR  - R01 MH068366/MH/NIMH NIH HHS/United States
GR  - R01 MH053484-11/MH/NIMH NIH HHS/United States
GR  - R01 MH068366-04/MH/NIMH NIH HHS/United States
GR  - P30 AI036214/AI/NIAID NIH HHS/United States
GR  - R01 MH68366-04/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080220
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 0 (Dopamine Agonists)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Dopamine)
RN  - N21FAR7B4S (Apomorphine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Acoustic Stimulation
MH  - Animals
MH  - Apomorphine/*pharmacology
MH  - Attention/drug effects
MH  - *Cues
MH  - Dopamine/metabolism
MH  - Dopamine Agonists/*pharmacology
MH  - Gene Expression/*drug effects
MH  - Neural Inhibition/*drug effects
MH  - Nucleus Accumbens/*drug effects
MH  - Oligonucleotide Array Sequence Analysis
MH  - Phenotype
MH  - RNA, Messenger/*genetics
MH  - Rats
MH  - Rats, Long-Evans
MH  - Rats, Sprague-Dawley
MH  - Receptors, Dopamine/*drug effects/*genetics
MH  - Reflex, Startle/*drug effects
MH  - Signal Transduction/*drug effects
MH  - Species Specificity
MH  - Transcription, Genetic/drug effects
PMC - PMC2771724
MID - NIHMS45325
EDAT- 2007/12/18 09:00
MHDA- 2008/04/15 09:00
PMCR- 2009/11/02
CRDT- 2007/12/18 09:00
PHST- 2007/08/22 00:00 [received]
PHST- 2007/10/09 00:00 [revised]
PHST- 2007/10/17 00:00 [accepted]
PHST- 2007/12/18 09:00 [pubmed]
PHST- 2008/04/15 09:00 [medline]
PHST- 2007/12/18 09:00 [entrez]
PHST- 2009/11/02 00:00 [pmc-release]
AID - S0006-3223(07)01035-9 [pii]
AID - 10.1016/j.biopsych.2007.10.015 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2008 Apr 15;63(8):748-58. doi: 10.1016/j.biopsych.2007.10.015. 
      Epub 2008 Feb 20.