Open AccessPhosphodiesterase‐1b deletion confers depression‐like behavioral resistance separate from stress‐related effects in mice
Author(s) -
Hufgard J. R.,
Williams M. T.,
Vorhees C. V.
Publication year - 2017
Publication title -
genes, brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.315
H-Index - 91
eISSN - 1601-183X
pISSN - 1601-1848
DOI - 10.1111/gbb.12391
Subject(s) - anhedonia , dentate gyrus , striatum , phenotype , phosphodiesterase , endocrinology , learned helplessness , behavioural despair test , medicine , imipramine , hippocampus , knockout mouse , antidepressant , psychology , serotonergic , neuroscience , substantia nigra , biology , pharmacology , serotonin , genetics , biochemistry , gene , developmental psychology , receptor , enzyme , dopaminergic , dopamine , alternative medicine , pathology
Phosphodiesterase‐1b (Pde1b) is highly expressed in striatum, dentate gyrus, CA3 and substantia nigra. In a new Floxed Pde1b × Cre CMV global knockout ( KO ) mouse model, we show an immobility‐resistance phenotype that recapitulates that found in constitutive Pde1b KO mice. We use this new mouse model to show that the resistance to acute stress‐induced depression‐like phenotype is not the product of changes in locomotor activity or reactivity to other stressors (learned helplessness, novelty suppressed feeding or dexamethasone suppression), and is not associated with anhedonia using the sucrose preference test. Using tamoxifen inducible Cre, we show that the immobility‐resistant phenotype depends on the age of induction. The effect is present when Pde1b is Reduced from conception, P0 or P32 , but not if reduced as adults ( P60 ). We also mapped regional brain expression of PDE1B protein and of the Cre driver. These data add to the suggestion that PDE1B may be a target for drug development with therapeutic potential in depression alone or in combination with existing antidepressants.