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

Abstract

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.

The effects of acute social isolation on long-term social recognition memory

“…Paired t-test: ⁄⁄ p < 0.001, ⁄ p < 0.05. on human mental health. Such a progress, coupled with experiments in other animal models, for example voles, (Lieberwirth, Liu, Jia, & Wang, 2012;Pournajafi-Nazarloo et al, 2011), would facilitate clinical trials with various interventions, such as intranasal delivery of oxytocin and vasopressin, to compensate for the damaging effects of social isolation. Moreover, these mechanisms may be relevant to other psycho-social diseases in which oxytocin and vasopressin may be involved, such as autism and schizophrenia (Harony & Wagner, 2010;MacDonald & Feifel, 2013).…”

The Neuroendocrinology of Social Isolation

“…Studies in monogamous prairie voles, for instance, show that a single acute (e.g., one hour) or repeated acute (e.g., one hour per day for four weeks) social isolation from a group or from a same-sex sibling increases corticosterone levels (e.g., Pournajafi-Nazarloo & Partoo 2011). This finding is in line with a large body of studies describing the separation of an animal from conspecifics as a stressor (Garrido et al 2012; Zlatković & Filipović 2012, 2013).…”

“…Pournajafi-Nazarloo & Partoo 2011). There are two important factors to consider in this literature, however.…”

Voluntary locomotor activity mitigates oxidative damage associated with isolation stress in the prairie vole (Microtus ochrogaster)

“…We designed a factorial experiment with two levels of locomotor activity (sedentary (S) and voluntary wheel running (W)) and two types of social environment (isolation (I) and pair housed (P)), since isolation in prairie voles results in social stress and increased glucocorticoid levels [2]. Seven of the 21 sibling pairs (n ¼ 14 individuals) were pair housed, not handled for the duration of the experiment and served as an unmanipulated control.…”

“…For animals characterized by structured group living however, social isolation is a potent stressor, as individual survival is dependent on the group [1], and separation results in a glucocorticoid stress response [2]. Increased levels of glucocorticoids have recently been linked with increased levels of oxidative stress [3,4].…”