Social isolation alters behavior, the gut-immune-brain axis, and neurochemical circuits in male and female prairie voles

Consequences of pandemic-associated social restrictions: Role of social support and the oxytocin system

“…In support of human studies, in laboratory animals including rats, mice and prairie voles, prolonged periods of social isolation (2 to 9 weeks in rodents) were found to increase emotional reactivity to stress, depressive-and anxiety-like behavior ( Donovan et al, 2020 , Grippo et al, 2011 ), aggression ( Donovan et al, 2020 , Haller et al, 2014 , Matsumoto et al, 2005 , Oliveira et al, 2019 , Ross et al, 2019 ), to impair social affiliation, and to induce cognitive deficits ( Fone and Porkess, 2008 , Ieraci et al, 2016 , Pereda-Pérez et al, 2013 , Pohl et al, 2019 ). Social isolation for several days or weeks also led to a dysregulation of the HPA axis, including an increased sensitivity of the pituitary corticotropic cells to corticotropin-releasing factor (CRF), increased adrenal response to acute stressors and impaired negative feedback in a sex-dependent manner resulting in a higher circulating corticosterone levels and increased susceptibility to subsequent acute stressors ( Bosch et al, 2009 , Donovan et al, 2020 , Gądek-Michalska et al, 2019 , Mumtaz et al, 2018 , Ohline and Abraham, 2019 , Serra et al, 2005 , Takatsu-Coleman et al, 2013 , Weintraub et al, 2010 , Weiss et al, 2004 ).…”

“…At brain level, impaired neurogenesis ( Dunphy-Doherty et al, 2018 ) and alterations in neuronal activity, microgliosis and BDNF expression in distinct regions of the social network, such as the hippocampus, Nucleus accumbens (NAc), amygdala, hypothalamus and prefrontal cortex (PFC) were found in rats, mice and prairie voles after social isolation ( Donovan et al, 2020 , Ieraci et al, 2016 , O'Keefe et al, 2014 ). Given their substantial role in modulating social and emotional behaviors it is not surprising that neuropeptide systems, such as arginine vasopressin (AVP), OXT, CRF, angiotensin II and tachykinin 2, were found to be profoundly affected by social isolation in a sex-dependent manner with respect to peptide or peptide receptor expression ( Armando et al, 2001 , Harvey et al, 2019 , Ieraci et al, 2016 , Oliveira et al, 2019 , Pan et al, 2009 , Pournajafi-Nazarloo et al, 2011 , Senst et al, 2016 , Zelikowsky et al, 2018 , Matthews and Tye, 2019 ).…”

Age-Related Individual Behavioural Characteristics of Adult Wistar Rats

“…If we assume that by the age of 2 months the main neurochemical systems that support motor activity and facilitate anxiety are formed, then we can surmise that the decrease in activity and increase in anxiety by the fifth month is associated with social influences occurring during this interval. Indeed, it has been shown that social isolation can increase the level of anxiety in animals [ 26 , 27 , 28 ] and in humans [ 29 ] and can have a significant effect on the level of motor activity. Thus, social isolation led to hyperactivity in males [ 30 , 31 , 32 ] and females [ 33 ].…”

The Long-Term Public Health Impact of Social Distancing on Brain Health: Topical Review

“…Older women are also more likely to be socially isolated based on census data demonstrating that, compared to men, women live alone more frequently [ 34 ]. In addition to higher risk for exposure to social isolation and loneliness in women, animal models suggest long-standing sex-dependent effects on abnormal gene expression in the brain related to neurological dysfunction [ 74 , 88 , 89 ].…”