Research article summary (published Dec 2007):

Behavioral characterization of mice deficient in the phosphodiesterase-10A (PDE10A) enzyme on a C57/Bl6N congenic background.

Full Abstract

The phenotype of genetically modified animals is strongly influenced by both the genetic background of the animal as well as environmental factors. We have previously reported the behavioral and neurochemical characterization of PDE10A knockout mice maintained on a DBA1LacJ (PDE10A(DBA)) genetic background. The aim of the present studies was to assess the behavioral and neurochemical phenotype of PDE10A knockout mice on an alternative congenic C57BL/6N (PDE10A(C57)) genetic background. Consistent with our previous results, PDE10A(C57) knockout mice showed a decrease in exploratory locomotor activity and a delay in the acquisition of conditioned avoidance responding. Also consistent with previous studies, the elimination of PDE10A did not alter basal levels of striatal cGMP or cAMP or affect behavior in several other well-characterized behavioral assays. PDE10A(C57) knockout mice showed a blunted response to MK-801, although to a lesser degree than previously observed in the PDE10A(DBA) knockout mice, and no differences were observed following a PCP challenge. PDE10A(C57) knockout mice showed a significant change in striatal dopamine turnover, which was accompanied by an enhanced locomotor response to AMPH, These studies demonstrate that while many of the behavioral effects of the PDE10A gene deletion appear to be independent of genetic background, the impact of the deletion on behavior can vary in magnitude. Furthermore, the effects on the dopaminergic system appear to be background-dependent, with significant effects observed only in knockout mice on the C57BL6N genetic background.

Author information

Author/s: Siuciak, Judith A (JA); McCarthy, Sheryl A (SA); Chapin, Douglas S (DS); Martin, Ashley N (AN); Harms, John F (JF); Schmidt, Christopher J (CJ);

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

Journal and publication information

Publication Type: Journal Article

Journal: Neuropharmacology (Neuropharmacology), published in England. (Language: eng)

Reference: 2008-Feb; vol 54 (issue 2) : pp 417-27

Dates: Created 2008/01/21; Completed 2008/05/12; Revised 2008/11/21;

PMID: 18061215, 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.

Amphetamine - pharmacology Animals Anxiety - psychology Avoidance Learning - drug effects; physiology Behavior, Animal - drug effects; physiology Biogenic Monoamines - metabolism Brain Chemistry - drug effects; genetics Chromatography, High Pressure Liquid Depression - psychology Dizocilpine Maleate - pharmacology Dopamine - metabolism Dopamine Uptake Inhibitors - pharmacology Excitatory Amino Acid Antagonists - pharmacology

Hot Temperature Methamphetamine - pharmacology Mice Mice, Inbred C57BL Mice, Knockout Motor Activity - drug effects Nucleotides, Cyclic - metabolism Pain Measurement - drug effects Phencyclidine - pharmacology Phosphoproteins - metabolism Phosphoric Diester Hydrolases - genetics; physiology Serotonin - metabolism Swimming - psychology

Associated Chemicals: Biogenic Monoamines (0) ; Dopamine Uptake Inhibitors (0) ; Excitatory Amino Acid Antagonists (0) ; Nucleotides, Cyclic (0) ; Phosphoproteins (0) ; Amphetamine (300-62-9) ; Serotonin (50-67-9) ; Dopamine (51-61-6) ; Methamphetamine (537-46-2) ; Phencyclidine (77-10-1) ; Dizocilpine Maleate (77086-22-7) ; Pde10a protein, mouse (EC 3.1.4.-) ; Phosphoric Diester Hydrolases (EC 3.1.4.-)

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