Negative social experiences such as social stressors and isolation influence mental and physical illnesses, including affective disorders and heart disease. Studies focused on socially monogamous prairie voles can provide insight into neurobiological systems that underlie the consequences of negative social interactions. Female prairie voles were exposed to 28 days of social isolation or pairing with a female sibling (control). Animals were administered daily oxytocin (20μg/50μl, sc) or saline vehicle (50μl, sc) for 14 days and exposed to two behavioral stressors (elevated plus maze and resident-intruder test). Brain tissue was collected for analysis of central peptide levels in the hypothalamic paraventricular nucleus. Isolation produced autonomic changes (increased heart rate, decreased heart rate variability) during both acute stressors, and increased anxiety behaviors in the elevated plus maze. Oxytocin prevented the autonomic consequences of the acute stressors in isolated prairie voles, but did not affect the behaviors tested under the present conditions. Oxytocin had no effect on the behavioral or autonomic responsiveness in paired prairie voles. Oxytocin may exert a beneficial effect on autonomic responses to stressors in isolated animals through increasing the numbers of oxytocin-containing neurons and decreasing the numbers of corticotropin-releasing hormone-containing neurons in the paraventricular nucleus. Oxytocinergic mechanisms may serve to compensate for autonomic responses associated with chronic isolation and exposure to both social and non-social acute stressors.

SummaryPrevious 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 1 hr (single isolation) or 1 hr 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.

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