Exposure to chronic isolation modulates receptors mRNAs for oxytocin and vasopressin in the hypothalamus and heart.

The goal of our study was to explore the effect of social isolation stress of varying durations on the plasma oxytocin (OT), messenger ribonucleic acid (mRNA) for oxytocin receptor (OTR), plasma arginine vasopressin (AVP) and mRNA for V1a receptor of AVP (V1aR) expression in the hypothalamus and heart of socially monogamous female and male prairie voles (Microtus ochrogaster). Continuous isolation for 4 weeks (chronic isolation) increased plasma OT level in females, but not in males. One hour of isolation every day for 4 weeks (repeated isolation) was followed by a significant increase in plasma AVP level. Chronic isolation, but not repeated isolation, significantly decreased OTR mRNA in the hypothalamus and heart in both sexes. Chronic isolation significantly decreased cardiac V1aR mRNA, but no effect on hypothalamic V1aR mRNA expression. We did not find a gender difference within repeated social isolation groups. The results of the present study reveal that although chronic social isolation can down-regulate gene expression for the OTR in both sexes, the release of the OT peptide was increased after chronic isolation only in females, possibly somewhat protecting females from the negative consequences of isolation. In both sexes repeated, but not chronic, isolation increased plasma AVP, which could be permissive for mobilization and thus adaptive in response to a repeated stressor. The differential effects of isolation on OT and AVP systems may help in understanding mechanisms through social interactions can be protective against emotional and cardiovascular disorders.

Effects of social isolation on mRNA expression for corticotrophin-releasing hormone receptors in prairie voles.

Previous studies have demonstrated that various type of stressors modulate messenger ribonucleic acid (mRNA) for type 1 corticotropin-releasing hormone (CRH) receptor (CRH-R1 mRNA) and type 2 CRH receptor (CRH-R2 mRNA). The purpose of this study was to explore the effect of social isolation stress of varying durations on the CRH, CRH-R1 and CRH-R2 mRNAs expression in the hypothalamus, hippocampus and pituitary of socially monogamous female and male prairie voles (Microtus ochrogaster). Isolation for 1h (single isolation) or 1h of isolation every day for 4 weeks (repeated isolation) was followed by a significant increase in plasma corticosterone levels. Single or repeated isolation increased hypothalamic CRH mRNA expression, but no changes in CRH-R1 mRNA in the hypothalamus were observed. Continuous isolation for 4 weeks (chronic isolation) showed no effect on hypothalamic CRH or CRH-R1 mRNAs in female or male animals. However, hypothalamic CRH-R2 mRNA was significantly reduced in voles exposed to chronic isolation. Single or repeated isolation, but not chronic isolation, significantly increased CRH-R1 mRNA and decreased CRH-R2 mRNA in the pituitary. Despite elevated CRH mRNA expression, CRH-R1 and CRH-R2 mRNAs were not modulated in the hippocampus following single or repeated isolation. Although, chronic isolation did not affect hippocampal CRH or CRH-R1 mRNAs, it did increase CRH-R2 mRNA expression in females and males. The results of the present study in prairie voles suggest that social isolation has receptor subtype and species-specific consequences for the modulation of gene expression for CRH and its receptors in brain and pituitary. Previous studies have revealed a female-biased increase in oxytocin in response to chronic isolation; however, we did not find a sex difference in CRH or its receptors following single, repeated or chronic social isolation, suggesting that sexually dimorphic processes beyond the CRH system, possibly involving vasopressin, might explain this difference.