Depression-Like Behavioral Phenotypes by Social and Social Plus Visual Isolation in the Adult Female Macaca fascicularis

Abstract

Major depressive disorder (MDD) is a debilitating psychiatric mood disorder that affects millions of individuals globally. Our understanding of the biological basis of MDD is poor, and current treatments are ineffective in a significant proportion of cases. This current situation may relate to the dominant rodent animal models of depression, which possess translational limitations due to limited homologies with humans. Therefore, a more homologous primate model of depression is needed to advance investigation into the pathophysiological mechanisms underlying depression and to conduct pre-clinical therapeutic trials. Here, we report two convenient methods – social isolation and social plus visual isolation – which can be applied to construct a non-human primate model of depression in the adult female cynomolgus monkey (Macaca fascicularis). Both social and social plus visual isolation were shown to be effective in inducing depression-like behavior by significantly reducing socially dominant aggressive conflict behavior, communicative behavior, sexual behavior, and parental behavior. The addition of visual isolation produced more profound behavioral changes than social isolation alone by further reducing parental behavior and sexual behavior. Thus, the degree of behavioral pathology may be manipulated by the degree of isolation. These methods can be applied to construct a non-human primate model of depression in order to assess physiological, behavioral, and social phenomena in a controlled laboratory setting.

Naltrexone treatment reverses astrocyte atrophy and immune dysfunction in self-harming macaques

“…Unlike other animal models, SIB and depressive-like behaviors in nonhuman primates can develop through social subordination and chronic social isolation (Gilmer and McKinney, 2003; Li et al, 2013). The severity of SIB in rhesus macaques ranges from biting that may not result in trauma to the skin to significant self-injury (Li et al, 2013; Willard et al, 2013).…”

“…Unlike other animal models, SIB and depressive-like behaviors in nonhuman primates can develop through social subordination and chronic social isolation (Gilmer and McKinney, 2003; Li et al, 2013). The severity of SIB in rhesus macaques ranges from biting that may not result in trauma to the skin to significant self-injury (Li et al, 2013; Willard et al, 2013). Furthermore, rhesus monkeys with SIB preferentially harm areas that are associated with acupuncture/acupressure analgesia (Marinus, 2000), an effect that has also been demonstrated in human self-injury (Symons and Thompson, 1997).…”

Toward a neurology of loneliness.

“…Among the adult vertebrate models of social isolation are voles (Fowler, Liu, Ouimet, & Wang, 2002; Grippo, Cushing, & Carter 2007; Grippo, Gerena, & Huang, 2007; Lieberwirth, Liu, Jia, & Wang, 2012; Pournajafi-Nazarloo & Partoo, 2011), gerbils (Ågren & Meyerson, 1978; Pickles, Hagan, Jones, & Hendrie, 2012), canaries (Lehongre, Aubin, & Del Negro, 2009; Terleph, Lu, & Vicario, 2008), zebra finches (Banerjee & Adkins-Regan, 2011; Barnea, Mishal, & Nottebohm, 2006; Lipkind, Nottebohm, Rado, & Barnea, 2002; Terleph et al, 2008), and nonhuman primates (e.g., Coelho, Carey, & Shade, 1991; Eaton, Kelley, Axthelm, Iliff-Sizemore, & Shiigi, 1994; Gilbert & Baker, 2011; Gust, Gordon, Brodie, & McGuire 1994; Gust, Gordon, & Hambright, 1993; Li et al, 2013; Niehoff, Bergmann, & Weinbauer, 2010; Sapolsky, Alberts, & Altmann, 1997; Shively, Clarkson, & Kaplan, 1989; Shively et al, 2005; A. S. Smith, Birnie, & French, 2011; T.…”

“…Socially isolated, compared to normally housed, nonhuman primates were characterized by (a) elevated hypothalamic pituitary adrenocortical activity, as indexed by basal hypercortisolism (Sapolsky et al, 1997), a rise of salivary cortisol levels (Cross, Pines, & Rogers, 2004), and urinary cortisol excretion (A. S. Smith et al, 2011; T. E. Smith & French, 1997); (b) greater depressive-like behavior (Li et al, 2013; Shively et al, 2005; Suomi et al, 1975); and (c) lower heart rates and higher blood pressure. In an interesting variation on this study design, Coelho et al (1991) measured cardiovascular activity in adult male baboons when they were housed (a) individually (Weeks 1 and 4); (b) with two socially familiar companions (i.e., the experimental animal had at least 4 years of previously established and nonhostile history with the companion; Weeks 2 and 5); and (c) with two socially unfamiliar animals (Weeks 3 and 6).…”

Self‐injurious behaviours in rhesus macaques: Potential glial mechanisms

“…An important caveat in these studies is the retrospective nature of the studies. It would be very interesting to repeat these studies using an induced depressive behaviour model (Li et al 2013) with age and social hierarchy matched animals with no history of self-injury. Further investigation is needed to determine precisely which cells are activated, and if treatment with antidepressants reverse all the components of the activation observed (Lee et al 2015a).…”