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Forschungsdatenbank PMU-SQQUID

Anxiety- rather than depression-like behavior is associated with adult neurogenesis in a female mouse model of higher trait anxiety- and comorbid depression-like behavior.
Sah, A; Schmuckermair, C; Sartori, SB; Gaburro, S; Kandasamy, M; Irschick, R; Klimaschewski, L; Landgraf, R; Aigner, L; Singewald, N
Transl Psychiatry. 2012; 2:e171
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Aigner Ludwig

Abstract

Adult neurogenesis has been implicated in affective disorders and the action of antidepressants (ADs) although the functional significance of this association is still unclear. The use of animal models closely mimicking human comorbid affective and anxiety disorders seen in the majority of patients should provide relevant novel information. Here, we used a unique genetic mouse model displaying higher trait anxiety (HAB) and comorbid depression-like behavior. We demonstrate that HABs have a lower rate of hippocampal neurogenesis and impaired functional integration of newly born neurons as compared with their normal anxiety/depression-like behavior (NAB) controls. In HABs, chronic treatment with the AD fluoxetine alleviated their higher depression-like behavior and protected them from relapse for 3 but not 7 weeks after discontinuation of the treatment without affecting neurogenesis. Similar to what has been observed in depressed patients, fluoxetine treatment induced anxiogenic-like effects during the early treatment phase in NABs along with a reduction in neurogenesis. On the other hand, treatment with AD drugs with a particularly strong anxiolytic component, namely the neurokinin-1-receptor-antagonist L-822 429 or tianeptine, increased the reduced rate of neurogenesis in HABs up to NAB levels. In addition, challenge-induced hypoactivation of dentate gyrus (DG) neurons in HABs was normalized by all three drugs. Overall, these data suggest that AD-like effects in a psychopathological mouse model are commonly associated with modulation of DG hypoactivity but not neurogenesis, suggesting normalization of hippocampal hypoactivity as a neurobiological marker indicating successful remission. Finally, rather than to higher depression-related behavior, neurogenesis seems to be linked to pathological anxiety.


Useful keywords (using NLM MeSH Indexing)

Analysis of Variance

Animals

Antidepressive Agents/pharmacology*

Antidepressive Agents/therapeutic use

Anxiety/complications

Anxiety/drug therapy

Anxiety/physiopathology*

Behavior, Animal

Biomarkers

Dentate Gyrus/drug effects*

Dentate Gyrus/pathology

Depression/complications

Depression/drug therapy

Depression/physiopathology*

Disease Models, Animal

Female

Fluoxetine/pharmacology*

Fluoxetine/therapeutic use

Mice

Neurogenesis/drug effects*

Piperidines/pharmacology

Recurrence

Remission Induction

Thiazepines/pharmacology


Find related publications in this database (Keywords)

animal model of anxiety and depression
antidepressants
IEG mapping
neurogenesis
remission and relapse