Research article summary (published 29 Nov 2007):

Behavioral and neurochemical characterization of mice deficient in the phosphodiesterase-4B (PDE4B) enzyme.

Full Abstract

RATIONALE: Phosphodiesterases (PDEs) belonging to the PDE4 family control intracellular concentrations of cyclic adenosine monophosphate (cAMP) by catalyzing its hydrolysis. Four separate PDE4 genes (PDE4A, PDE4B, PDE4C, and PDE4D) have been identified. PDE4 has been reported to be involved in various central nervous system (CNS) functions including depression, memory, and schizophrenia, although the specific subtype mediating these effects remains unclear. OBJECTIVE: To investigate the role of PDE4B in the CNS, PDE4B wild-type and knockout mice (C57BL/6N background) were assessed in a variety of well-characterized behavioral tasks, and their brains were assayed for monoamine content. RESULTS: Knockout mice showed a significant reduction in prepulse inhibition. Spontaneous locomotor activity was decreased (16%) in knockout mice. Furthermore, when challenged with amphetamine, both groups of mice responded similarly to a low dose of d-amphetamine (1.0 mg/kg), but knockout mice showed an enhanced response to a higher dose (1.78 mg/kg). Decreases in baseline levels of monoamines and their metabolites within the striatum of knockout mice were also observed. PDE4B knockout mice showed a modest decrease in immobility time in the forced swim test that approached significance. In several other tests, including the elevated plus maze, hot plate, passive avoidance, and Morris water maze, wild-type and knockout mice performed similarly. CONCLUSION: The present studies demonstrate decreased striatal DA and 5-HT activity in the PDE4B knockout mice associated with decreased prepulse inhibition, decreased baseline motor activity, and an exaggerated locomotor response to amphetamine. These data further support a role for PDE4B in psychiatric diseases and striatal function.

Author information

Author/s: Siuciak, Judith A (JA); McCarthy, Sheryl A (SA); Chapin, Douglas S (DS); Martin, Ashley N (AN);

Affiliation: CNS Discovery Research, Pfizer Global Research & Development, Groton, CT, 06340, USA. judith.siuciak(-atsign-)bms.com

Journal and publication information

Publication Type: Journal Article

Journal: Psychopharmacology (Psychopharmacology (Berl)), published in Germany. (Language: eng)

Reference: 2008-Mar; vol 197 (issue 1) : pp 115-26

Dates: Created 2008/03/19; Completed 2008/08/29;

PMID: 18060387, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Arousal - drug effects; physiology Behavior, Animal - drug effects; physiology Brain - drug effects; physiopathology Cyclic Nucleotide Phosphodiesterases, Type 4 - genetics Dextroamphetamine - pharmacology Dopamine - metabolism Dose-Response Relationship, Drug

Male Mice Mice, Inbred C57BL Mice, Knockout Motivation Motor Activity - drug effects; physiology Serotonin - metabolism Startle Reaction - drug effects; physiology

Associated Chemicals: Serotonin (50-67-9) ; Dopamine (51-61-6) ; Dextroamphetamine (51-64-9) ; Cyclic Nucleotide Phosphodiesterases, Type 4 (EC 3.1.4.17)

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