1. Early life stress alters adult serotonin 2C receptor pre-mRNA editing and expression of the alpha subunit of the heterotrimeric G-protein G q.
- Author
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Bhansali P, Dunning J, Singer SE, David L, and Schmauss C
- Subjects
- Age Factors, Animals, Anxiety, Separation complications, Anxiety, Separation psychology, Body Weight, Depressive Disorder drug therapy, Depressive Disorder etiology, Depressive Disorder physiopathology, Depressive Disorder psychology, Emotions, Environment, Female, Fluoxetine pharmacology, Fluoxetine therapeutic use, GTP-Binding Protein alpha Subunits, Gq-G11 biosynthesis, Genetic Predisposition to Disease, Helplessness, Learned, Male, Mice, Mice, Inbred BALB C genetics, Mice, Inbred BALB C psychology, Mice, Inbred C57BL, Neocortex metabolism, Protein Isoforms biosynthesis, Protein Isoforms genetics, Protein Isoforms physiology, Random Allocation, Receptor, Serotonin, 5-HT2C biosynthesis, Receptor, Serotonin, 5-HT2C physiology, Selective Serotonin Reuptake Inhibitors pharmacology, Selective Serotonin Reuptake Inhibitors therapeutic use, Species Specificity, Swimming, Anxiety, Separation genetics, Depressive Disorder genetics, GTP-Binding Protein alpha Subunits, Gq-G11 genetics, Mice, Inbred BALB C physiology, RNA Editing, RNA Precursors genetics, Receptor, Serotonin, 5-HT2C genetics, Serotonin physiology
- Abstract
Infant maternal separation, a paradigm of early life stress in rodents, elicits long-lasting changes in gene expression that persist into adulthood. In BALB/c mice, an inbred strain with spontaneously elevated anxiety and stress reactivity, infant maternal separation led to increased depression-like behavioral responses to adult stress and robustly increased editing of serotonin 2C receptor pre-mRNA. Chronic fluoxetine treatment of adult BALB/c mice exposed to early life stress affected neither their behavioral responses to stress nor their basal 5-HT2C pre-mRNA editing phenotype. However, when fluoxetine was administered during adolescence, depression-like behavioral responses to stress were significantly diminished in these mice, and their basal and stress-induced 5-HT2C pre-mRNA editing phenotypes were significantly lower. Moreover, when BALB/c mice exposed to early life stress were raised in an enriched postweaning environment, their depression-like behavioral responses to adult stress were also significantly diminished. However, their 5-HT2C pre-mRNA editing phenotype remained unaltered. Hence, the similar behavioral effects of enrichment and fluoxetine treatment during adolescence were not accompanied by similar changes in 5-HT2C pre-mRNA editing. Enriched and nonenriched BALB/c mice exposed to early life stress also exhibited significantly increased expression of mRNA and protein encoding the G alpha q subunit of G-protein that couples to 5-HT2A/2C receptors. In contrast, G alpha q expression levels were significantly lower in fluoxetine-treated mice. These findings suggest that compensatory changes in G alpha q expression occur in mice with persistently altered 5-HT2C pre-mRNA editing and provide an explanation for the dissociation between 5-HT2C receptor editing phenotypes and behavioral stress responses.
- Published
- 2007
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