Behavioral characterization of mice deficient in the phosphodiesterase-10A (PDE10A) enzyme on a C57/Bl6N congenic background.
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.
Siuciak
Judith A
JA
Neuroscience, Pfizer Global Research & Development, Groton, CT, USA. judith.siuciak@bms.com
McCarthy
Sheryl A
SA
Chapin
Douglas S
DS
Martin
Ashley N
AN
Harms
John F
JF
Schmidt
Christopher J
CJ
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000523:psychology; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D015306:Biogenic Monoamines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D003863:Depression / Q000523:psychology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006358:Hot Temperature; D008694:Methamphetamine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D009712:Nucleotides, Cyclic / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects; D010622:Phencyclidine / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000235:genetics* / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D013550:Swimming / Q000523:psychology
D015306:Biogenic Monoamines; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D009712:Nucleotides, Cyclic; D010750:Phosphoproteins; D012701:Serotonin; D008694:Methamphetamine; D016291:Dizocilpine Maleate; D000661:Amphetamine; C492284:Pde10a protein, mouse; D010727:Phosphoric Diester Hydrolases; D010622:Phencyclidine; D004298:Dopamine