PMID- 22487514
OWN - NLM
STAT- MEDLINE
DCOM- 20121120
LR  - 20211021
IS  - 1601-183X (Electronic)
IS  - 1601-1848 (Print)
IS  - 1601-183X (Linking)
VI  - 11
IP  - 5
DP  - 2012 Jul
TI  - A new model of Pde4d deficiency: genetic knock-down of PDE4D enzyme in rats 
      produces an antidepressant phenotype without spatial cognitive effects.
PG  - 614-22
LID - 10.1111/j.1601-183X.2012.00796.x [doi]
AB  - Phosphodiesterases (PDEs) are a superfamily of intracellular second messenger 
      cyclic nucleotide hydrolyzing enzymes composed of 12 families. The Pde4 family 
      has been implicated in depression and cognition, and PDE4 inhibitors have been 
      evaluated as antidepressants and possible cognitive enhancers. Pde4d(-/-) mice 
      show an antidepressant phenotype and learning enhancement on some tests, but not 
      others as do mice treated with PDE4 inhibitors. Here, we report for the first 
      time the behavioral phenotype of a new Pde4d knock-down (KD) rat model of PDE4D 
      deficiency. Consistent with other data on PDE4D deficiency, Pde4d KD rats showed 
      depression resistance in the Porsolt forced swim test and hyperreactivity of the 
      acoustic startle response with no differential response on prepulse inhibition, 
      suggesting no sensorimotor gating defect. Pde4d KD rats also exhibited a small 
      exploratory activity reduction but no difference following habituation, and no 
      enhanced spatial learning or reference memory in the Morris water maze. A 
      selective improvement in route-based learning in the Cincinnati water maze was 
      seen as well as enhanced contextual and cued fear conditioning and a more rapid 
      rate of cued extinction from their higher freezing level that declined to 
      wild-type (WT) levels only after  approximately 20 extinction trials. The rat model confirms 
      Pde4d's role in depression but not in spatial learning or memory enhancement and 
      shows for the first time higher fear conditioning and altered extinction compared 
      with controls. The new model provides a tool by which to better understand the 
      role of PDE4D in neuropsychiatric disorders and for the development of alternate 
      treatment approaches.
CI  - (c) 2012 The Authors. Genes, Brain and Behavior (c) 2012 Blackwell Publishing Ltd and 
      International Behavioural and Neural Genetics Society.
FAU - Schaefer, T L
AU  - Schaefer TL
AD  - Division of Neurology, Department of Pediatrics, Cincinnati Children's Research 
      Foundation and University of Cincinnati College of Medicine, OH 45229-3039, USA.
FAU - Braun, A A
AU  - Braun AA
FAU - Amos-Kroohs, R M
AU  - Amos-Kroohs RM
FAU - Williams, M T
AU  - Williams MT
FAU - Ostertag, E
AU  - Ostertag E
FAU - Vorhees, C V
AU  - Vorhees CV
LA  - eng
GR  - R01 DA006733/DA/NIDA NIH HHS/United States
GR  - T32 ES007051/ES/NIEHS NIH HHS/United States
GR  - ES007051/ES/NIEHS NIH HHS/United States
GR  - DA006733/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120508
PL  - England
TA  - Genes Brain Behav
JT  - Genes, brain, and behavior
JID - 101129617
RN  - EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 3)
RN  - EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 4)
RN  - EC 3.1.4.17 (PDE4D protein, rat)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/physiology
MH  - Brain/enzymology
MH  - Conditioning, Classical/physiology
MH  - Cyclic Nucleotide Phosphodiesterases, Type 3/*genetics/metabolism
MH  - Cyclic Nucleotide Phosphodiesterases, Type 4
MH  - Depression/*enzymology/genetics
MH  - Disease Models, Animal
MH  - Exploratory Behavior/physiology
MH  - Extinction, Psychological/physiology
MH  - Fear/physiology
MH  - Maze Learning/*physiology
MH  - Motor Activity/genetics
MH  - Rats
MH  - Reflex, Startle/genetics
PMC - PMC4511101
MID - NIHMS368703
COIS- Author Conflict of Interest Statement TLS, AAB, RMAK, MTW, and CVV declare no 
      conflict of interest. EO is President and CEO of Transposagen Biopharmaceutical 
      Company that provided the gene-targeted animals for this project.
EDAT- 2012/04/11 06:00
MHDA- 2012/12/10 06:00
PMCR- 2015/07/22
CRDT- 2012/04/11 06:00
PHST- 2012/04/11 06:00 [entrez]
PHST- 2012/04/11 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
PHST- 2015/07/22 00:00 [pmc-release]
AID - 10.1111/j.1601-183X.2012.00796.x [doi]
PST - ppublish
SO  - Genes Brain Behav. 2012 Jul;11(5):614-22. doi: 10.1111/j.1601-183X.2012.00796.x. 
      Epub 2012 May 8.