Levels of phosphodiesterase 4A and 4B are altered by chronic treatment with psychotropic medications in rat frontal cortex

Our laboratory has recently demonstrated altered expression of phosphodiesterase (PDE) 4A and 4B in subjects with autism, bipolar disorder, and schizophrenia, suggesting disrupted cAMP signaling in these diagnostic groups. In the current study, we measured expression of PDEs in rat frontal cortex (F...

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Published in:Synapse (New York, N.Y.) N.Y.), 2010-07, Vol.64 (7), p.550-555
Main Authors: Fatemi, S. Hossein, Folsom, Timothy D., Reutiman, Teri J., Braun, Natalie N., Lavergne, Luke G.
Format: Article
Language:English
Subjects:
3',5'-Cyclic-AMP Phosphodiesterases - metabolism
Animals
Autism
Bipolar disorder
Blotting, Western
Ca super(2+)/calmodulin-dependent phosphodiesterase
Clozapine
Cortex (frontal)
Cyclic AMP
Cyclic Nucleotide Phosphodiesterases, Type 1 - metabolism
Cyclic Nucleotide Phosphodiesterases, Type 3 - metabolism
Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism
Electrophoresis, Polyacrylamide Gel
Fluoxetine
frontal cortex
Frontal Lobe - drug effects
Frontal Lobe - metabolism
Gene expression
Haloperidol
Lithium
Male
Mental disorders
mRNA
olanzapine
phosphodiesterase
phosphodiesterase 4A
phosphodiesterase 4B
Phosphoric Diester Hydrolases - metabolism
Psychotropic Drugs - administration & dosage
Psychotropic Drugs - pharmacology
Random Allocation
rat
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - metabolism
Schizophrenia
Synapses
Time Factors
Valproic acid
Western blotting
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Summary:Our laboratory has recently demonstrated altered expression of phosphodiesterase (PDE) 4A and 4B in subjects with autism, bipolar disorder, and schizophrenia, suggesting disrupted cAMP signaling in these diagnostic groups. In the current study, we measured expression of PDEs in rat frontal cortex (FC) following chronic treatment with clozapine, fluoxetine, haloperidol, lithium, olanzapine, valproic acid (VPA), or sterile saline for 21 days. Western blotting experiments showed decreased expression of PDE4A subtypes in FC following treatment with clozapine, haloperidol, lithium, and VPA. PDE4B subtypes were similarly reduced in FC following treatment with clozapine, fluoxetine, and lithium. We also measured levels of nine PDE subtypes via qRT‐PCR in FC and found significant upregulation of PDE1A and PDE8B following treatment with olanzapine, while treatment with lithium reduced expression of mRNA for PDE8B. Our results demonstrate altered expression of PDE4A and PDE4B in response to a variety of psychotropic medications suggesting potentially new therapeutic avenues for treatment of neuropsychiatric diseases. Synapse 64:550–555, 2010. © 2010 Wiley‐Liss, Inc.
ISSN:0887-4476
1098-2396
1098-2396
DOI:10.1002/syn.20762