A working model for the assessment of disruptions in social behavior among aged rats: The role of sex differences, social recognition, and sensorimotor processes

Abstract

Aging results in a natural decline in social behavior, yet little is known about the processes underlying these changes. Engaging in positive social interaction is associated with many health benefits, including reduced stress reactivity, and may serve as a potential buffer against adverse consequences of aging. The goal of these studies was to establish a tractable model for the assessment of social behavior deficits associated with late aging. Thus, in Exp. 1, 1.5-, 3-, and 18-month-old male Fischer 344 (F344) rats were assessed for object investigation, and social interaction with a same-aged partner (novel/familiar), or a different-aged partner, thereby establishing working parameters for studies that followed. Results revealed that 18-month-old males exhibited reductions in social investigation and social contact behavior, with this age-related decline not influenced by familiarity or age of the social partner. Subsequently, Exp. 2 extended assessment of social behavior to both male and female F344 rats at multiple ages (3, 9, 18, and 24 months), after which a series of sensorimotor performance tests were conducted. In this study, both males and females exhibited late aging-related reductions in social interactions, but these changes were more pronounced in females. Additionally, sensorimotor performance was shown to be impaired in 24-month-olds, but not 18-month-olds, with this deficit more evident in males. Finally, Exp. 3 examined whether aging-related inflammation could account for declines in social behavior during late aging by administering naproxen (0, 7, 14, and 28 mg/kg; s.c.)—a non-steroidal anti-inflammatory drug—to 18-month-old females. Results from this study revealed that social behavior was unaffected by acute or repeated (6 days) naproxen, suggesting that aging-related social deficits in females may not be a consequence of a general aging-related inflammation and/or malaise. Together, these findings demonstrate that aging-related declines in social behavior are (i) specific to social stimuli and (ii) not indicative of a general state of aging-related debilitation. Thus, these findings establish working parameters for a highly tractable model in which the neural and hormonal mechanisms underlying aging-related declines in social behavior can be examined.

Analysis of c-Fos induction in response to social interaction in male and female Fisher 344 rats

“…For instance, adult male Lister rats spend more time interacting with a familiar age-matched conspecific (Johnston and File, 1991) and adult male Sprague-Dawley rats (Stack et al, 2010; Varlinskaya et al, 2014) and Wistar rats (Dumais et al, 2013) engage in higher levels of active social interaction with a novel adult or juvenile conspecific (Dumais et al, 2013), relative to their female counterparts. We have shown previously that 3-month old male and female Fisher 344 (F344) rats exhibit similar levels of social investigation of novel and familiar social partners, with both sexes demonstrating a significant decline in social behavior during late aging (i.e., 18 months and beyond) (Perkins et al, 2016). Although F344 rats exhibit lower levels of social behavior relative to other strains (e.g.…”

“…However, much less is known about the neurobiology of adult responding to a same sex conspecific. Compared to adolescents, adults exhibit reduced levels of social behavior (Perkins et al, 2016). Adolescents also exhibit greater induction of c-Fos protein in response to a social partner in the amygdala (AMG) and BNST, whereas adults exhibit less c-Fos induction following a social interaction in the PFC, nucleus accumbens (NAC), and brainstem relative to their counterparts placed alone in the context (Varlinskaya et al, 2013).…”

Assessment of social behavior directed toward sick partners and its relation to central cytokine expression in rats

“…In young rodents, social behavior typically consists of social play and active investigation of a conspecific through sniffing and social contact behavior [8–11]. Using these rodent models, social processes have been shown to be easily disrupted by a wide variety of circumstances, including stress challenges [12, 13], natural aging [14] and acute illness [5, 6, 15, 16]. …”

“…housing conditions) of the experimental test subject also determines the level of social behavior expressed in subsequent, discrete tests of social interaction [27, 28]. For example, both short-term (not more than 24 h) and long-term (several days to several weeks) social deprivation have often been used to increase the frequency of social behavior exhibited during social testing [14, 28]. On the other hand, prolonged social deprivation can have seriously detrimental effects, particularly when the social deprivation is incurred during critical developmental epochs [29–31].…”

Effects of combined substance membratonon correction of theindicators of zoo-social behavior of old rats

“…It should be noted that complex behaviors, both social (social memory and social recognition, sexual and family behavior, social advantage, interspecific interaction), and non-social (learning, remembering) in animals also undergo a wide range of changes in aging [8]. Decreased sensory and motor functions and impaired coordination [9], increased anxiety [10], cognitive dysfunction associated with a gradual decrease in structural and functional plasticity in the hippocampus and prefrontal cortex [11] -these are just the main factors that influence the behavior of animals.…”