Two Chronic Stress Models Based on Movement Restriction in Rats Respond Selectively to Antidepressant Drugs: Aldolase C As a Potential Biomarker
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Two Chronic Stress Models Based on Movement Restriction in Rats Respond Selectively to Antidepressant Drugs: Aldolase C As a Potential Biomarker
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Abstract
Background: Clinically depressed individuals respond to different types of antidepressants, suggesting that different
neurobiological mechanisms may be responsible for their depression. However, animal models to characterize this are not
yet available.
Methods: We induced depressive-like behaviors in rats using 2 different chronic stress models: restraint in small cages or
immobilization in adaptable plastic cones. Both models increased anxiety responses evaluated by novelty-suppressed feeding
and the elevated plus-maze; increased learned helplessness evaluated by the tail suspension and forced swimming tests; and
increased anhedonia evaluated by the sucrose preference test.
Results: We assessed the ability of 2 different types of antidepressants to ameliorate depressive-like behaviors. We
administered the serotonin reuptake inhibitor fluoxetine or the noradrenaline reuptake inhibitor reboxetine once daily for
28 days to rats that received either chronic restraint or immobilization stress, or no stress. Behavioral analysis revealed that
fluoxetine ameliorated depressive-like behaviors when induced by chronic restraint stress, whereas reboxetine ameliorated
these behaviors when induced by chronic immobilization stress. To further test biological differences between both models,
we evaluated the levels of Aldolase C, an enzyme expressed by forebrain astrocytes that is regulated by antidepressant
treatment, in the cerebrospinal fluid: chronic restraint stress, but not immobilization stress, increased the levels of Aldolase
C. Moreover, the presence of astrocyte-derived Aldolase C-GFP in the cerebrospinal fluid indicates its central origin.
Conclusions: Two stress paradigms induced depressive-like behaviors that were sensitive to different antidepressant treatments.
Biomarkers such as Aldolase C could help determine optimal antidepressant treatments for clinically depressed patients.
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Conicyt (Fondecyt)
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International Journal of Neuropsychopharmacology Volumen: 18 Número: 10 Sep 2015
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