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The Journal of Neuroscience, February 7, 2007, 27(6):1467-1473; doi:10.1523/JNEUROSCI.4632-06.2007

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Neurobiology of Disease
Early Life Stress Alters Adult Serotonin 2C Receptor Pre-mRNA Editing and Expression of the Subunit of the Heterotrimeric G-Protein Gq

Punita Bhansali,^1,3 Jane Dunning,³ Sarah E. Singer,² Leora David,^1,3 and Claudia Schmauss^1,3

¹Department of Psychiatry and ²Center for Neurobiology and Behavior, Columbia University, and ³Department of Neuroscience, New York State Psychiatric Institute, New York, New York 10032

Correspondence should be addressed to Dr. Claudia Schmauss, Department of Psychiatry and Neuroscience, Columbia University and New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032. Email: schmauss{at}neuron.cpmc.columbia.edu

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-HT_2C 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-HT_2C 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-HT_2C 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-HT_2C 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 Gq subunit of G-protein that couples to 5-HT_2A/2C receptors. In contrast, Gq expression levels were significantly lower in fluoxetine-treated mice. These findings suggest that compensatory changes in Gq expression occur in mice with persistently altered 5-HT_2C pre-mRNA editing and provide an explanation for the dissociation between 5-HT_2C receptor editing phenotypes and behavioral stress responses.

Key words: early life stress; serotonin 2C receptor; RNA editing; G-protein; antidepressant drugs; environmental enrichment

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Received Aug. 4, 2006; revised Dec. 4, 2006; accepted Jan. 2, 2007.

Correspondence should be addressed to Dr. Claudia Schmauss, Department of Psychiatry and Neuroscience, Columbia University and New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032. Email: schmauss{at}neuron.cpmc.columbia.edu

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