24-Hour Autonomic Dysfunction and Depressive Behaviors in an Animal Model of Social Isolation: Implications for the Study of Depression and Cardiovascular Disease

Abstract

Objective-Converging evidence from both experimental and epidemiological studies indicates that there is a bidirectional association between depression and cardiovascular disease, however the precise neurobiological mechanisms underlying this relationship are not well understood. Disruptions in the social environment may influence this relationship. The primary objective of the present study was to investigate the hypothesis that long-term social isolation in an animal model would produce depression-relevant behaviors and disruptions in 24-hour autonomic and activity parameters, and to further demonstrate the utility and validity of an animal model for the study of the social environment, behavior, and autonomic function.Methods-Depression-relevant behaviors and ambulatory electrocardiographic and activity data were measured in 12 adult, socially monogamous prairie voles (rodents), during a period of chronic social isolation or social pairing (control conditions).Results-Prairie voles exposed to 4 weeks of social isolation, versus control conditions (social pairing), exhibited anhedonia, increased 24-hour heart rate, reduced 24-hour heart rate variability, and predictable correlations between the behavioral measure (anhedonia) and the autonomic measures.Conclusions-Social isolation is associated with depressive behaviors, 24-hour autonomic dysfunction, and predictable interrelationships between these variables in prairie voles, but does not appear to be associated with rhythmicity changes in activity level or autonomic function. These findings have implications for understanding the role of the social environment in mediating the association of mood and cardiovascular disorders in humans.

Differences in Titi Monkey (Callicebus cupreus) Social Bonds Affect Arousal, Affiliation, and Response to Reward

“…Social isolation has been utilized to act as a model of neuropsychiatric illnesses and is viewed as a chronic stressor. Social isolation results in negative affect, decreased body weight, and chronically high levels of glucocorticoids [Grippo et al 2011; Grippo et al 2007a; Grippo et al 2007b; Grippo et al 2007c; Grippo et al 2008; Kim and Kirkpatrick 1996; Panksepp 2003; Wallace et al 2009]. In prairie voles and rats, social isolation results in anhedonia reflected by a decrease in consumption of a sucrose solution and have been shown to be more behaviorally reactive to stressors such as resident-intruder tests and the elevated plus maze [Grippo et al 2007a; Grippo et al 2007b; Grippo et al 2007c; Grippo et al 2008; Wallace et al 2009].…”

Aversive motivation and the maintenance of monogamous pair bonding

“…For example, a lack of stable social bonds contributes to the development of mood disorders ( Cacioppo et al, 2002 ) and increases health problems, such as the risk of heart disease ( Carney et al, 1988 ;Pratt et al, 1996 ;Steptoe et al, 2004 ;Johnson and Grippo, 2006 ;Grippo et al, 2011 ). Importantly, recent work utilizing the prairie vole animal model of selective social attachment has allowed the neurobiology underlying these adverse social conditions to begin to unfold ( Grippo et al, 2007 ).…”

“…Importantly, recent work utilizing the prairie vole animal model of selective social attachment has allowed the neurobiology underlying these adverse social conditions to begin to unfold ( Grippo et al, 2007 ). In sexually na ï ve prairie voles, chronic isolation induces depressive-like symptoms that are correlated with changes in autonomic function and circulating levels of a hormone important for mediating stress responses, corticosterone ( Grippo et al, 2011 ). Additionally, short-term absence from a bonded partner in this species increases both anxiety and depressive-like symptoms that are mediated by the activation of corticotrophin-releasing factor (CRF) ( Bosch et al, 2009 ), a neural mediator of stress ( Hauger et al, 2009 ).…”

Acoustic features of prairie vole (Microtus ochrogaster) ultrasonic vocalizations covary with heart rate

“…These observations reflect the strong influence of myelinated vagal pathways on the heart of prairie voles. The robust vagal output inherent to the prairie vole produces large rhythmic beat-to-beat changes in heart rate in frequencies similar to spontaneous respiration (i.e., respiratory sinus arrhythmia, RSA) [14, 15]. The amplitude of RSA for prairie voles is in the range of humans and significantly higher than other laboratory rodents, such as mice and rats, which during basal state express high sympathetic tone and low vagal tone to the heart [14].…”

“…In addition, prairie voles are highly vocal, possessing a disproportionately large auditory cortex [16-18]. Thus, prairie voles, by expressing atypically strong vagal influences to the heart [14, 15, 19] and by being atypically vocal, offer significant translational potential for investigating a potential covariation between the regulation of vocalizations and heart rate.…”