Antidepressant treatment outcome depends on the quality of the living environment: a pre-clinical investigation in mice
| Autor: | Ivana D'Andrea, Sara Santarelli, Igor Branchi, Enrico Alleva, Francesca Cirulli, Sara Capoccia, S. Poggini |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
Genetics and Molecular Biology (all) Mouse Anhedonia Psychopharmacology Drug Evaluation Preclinical Pharmacology Social and Behavioral Sciences Inbred C57BL Biochemistry Behavioral Neuroscience chemistry.chemical_compound Mice 0302 clinical medicine Corticosterone Psychology Chronic stress Psychiatry Multidisciplinary Environmental Pharmacology Behavior Animal Brain Animal Models Antidepressive Agents Preclinical Mental Health Treatment Outcome Behavioral Pharmacology Serotonin Uptake Inhibitors Antidepressant Medicine medicine.symptom antidepressant SSRI fluoxetine environment life events major depression plasticity serotonin differential susceptibility Selective Serotonin Reuptake Inhibitors Research Article medicine.drug Drugs and Devices Serotonin Science Biology Environment Stress 03 medical and health sciences Model Organisms Neuropsychology Fluoxetine medicine Animals Brain-derived neurotrophic factor Depressive Disorder Major Environmental enrichment Behavior Depressive Disorder Mood Disorders Animal Brain-Derived Neurotrophic Factor Major 030227 psychiatry Mice Inbred C57BL chemistry Agricultural and Biological Sciences (all) Stress Psychological Biochemistry Genetics and Molecular Biology (all) Drug Evaluation Psychological 030217 neurology & neurosurgery Neuroscience |
| Zdroj: | PLoS ONE, Vol 8, Iss 4, p e62226 (2013) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Antidepressants represent the standard treatment for major depression. However, their efficacy is variable and incomplete. A growing number of studies suggest that the environment plays a major role in determining the efficacy of these drugs, specifically of selective serotonin reuptake inhibitors (SSRI). A recent hypothesis posits that the increase in serotonin levels induced by SSRI may not affect mood per se, but enhances neural plasticity and, consequently, renders the individual more susceptible to the influence of the environment. Thus, SSRI administration in a favorable environment would lead to a reduction of symptoms, while in a stressful environment might lead to a worse prognosis. To test this hypothesis, we treated C57BL/6 adult male mice with chronic fluoxetine while exposing them to either (i) an enriched environment, after exposure to a chronic stress period aimed at inducing a depression-like phenotype, or (ii) a stressful environment. Anhedonia, brain BDNF and circulating corticosterone levels, considered endophenotypes of depression, were investigated. Mice treated with fluoxetine in an enriched condition improved their depression-like phenotype compared to controls, displaying higher saccharin preference, higher brain BDNF levels and reduced corticosterone levels. By contrast, when chronic fluoxetine administration occurred in a stressful condition, mice showed a more distinct worsening of the depression-like profile, displaying a faster decrease of saccharin preference, lower brain BDNF levels and increased corticosterone levels. Our findings suggest that the effect of SSRI on depression-like phenotypes in mice is not determined by the drug per se but is induced by the drug and driven by the environment. These findings may be helpful to explain variable effects of SSRI found in clinical practice and to device strategies aimed at enhancing their efficacy by means of controlling environmental conditions. |
| Databáze: | OpenAIRE |
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