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Abstract

There is substantial evidence that early life events influence brain development and subsequent adult behavior and play an important role in the causation of certain psychiatric disorders including schizophrenia and depression. The underlying mechanism of the effects of these early environmental factors is still not understood. It is a challenge to attempt to model early environmental factors in animals to gain understanding of the basic mechanisms that underlie the long-term effects. This paper reviews the effects of rearing rats from weaning in social isolation and reports some recent results indicating hippocampal dysfunction. Isolation rearing in rats from weaning produces a range of persistent behavioral changes in the young adult, including hyperactivity in response to novelty and amphetamine and altered responses to conditioning. These are associated with alterations in the central aminergic neurotransmitter functions in the mesolimbic areas and other brain regions. Isolation-reared rats have enhanced presynaptic dopamine (DA) and 5-HT function in the nucleus accumbens (NAC) associated with decreased presynaptic 5-HT function in the frontal cortex and hippocampus. Isolation-reared rats have reduced presynaptic noradrenergic function in the hippocampus, but have enhanced presynaptic DA function in the amygdala. These neurochemical imbalances may contribute to the exaggerated response of the isolated rat to a novel stimulus or to stimuli predictive of danger, and isolation-induced behavioral changes. These changes have neuroanatomical correlates, changes which seem to parallel to a certain degree those seen in human schizophrenia. A greater understanding of the processes that underlie these changes should improve our knowledge of how environmental events may alter brain development and function, and play a role in the development of neuropsychiatric disorders.

Escalation of cocaine self-administration in adulthood after social defeat of adolescent rats: role of social experience and adaptive coping behavior

“…A different social defeat schedule, strain of rat, novel apparatuses, and different treatment of controls may account for the conflicting results. The increased locomotion for SH rats compared to PH rats agrees with other studies during adolescence (Levine et al 2007; Meng et al 2010) and adulthood (Chappell et al 2013; Lapiz et al 2003; Powell et al 2002; Wright et al 1991). Less time in the center of the open field of SH rats suggests greater anxiety (Prut and Belzung 2003) and replicates a previous report (Meng et al 2010).…”

Social Isolation Rearing Increases Nucleus Accumbens Dopamine and Norepinephrine Responses to Acute Ethanol in Adulthood

“…Social isolation for an extended period of time during adolescence, a form of chronic early-life stress, results in an increased locomotor response (Lapiz et al, 2003) and increased DA release in the NAc (Fabricius et al, 2011) following amphetamine administration. Cocaine also causes a sensitized locomotor response in SI rats (Phillips et al, 1994).…”

Consequences of post-weaning social isolation on anxiety behavior and related neural circuits in rodents

“…Isolation-reared rats are housed within the same holding room as group-reared control rats, with the latter typically housed in groups of three to five rats per cage. Thus, socially isolated rats are completely deprived of social contact but still have access to olfactory, auditory and visual cues from other rats within the holding room (Lapiz et al, 2003; Fone and Porkees, 2008). Environmental enrichment reverses some of the effects of post-weaning social isolation (Hellemans et al, 2004; Hoffmann et al, 2009), suggesting that enrichment should not be used for standard isolation procedures.…”

“…In the vast majority of post-weaning social isolation studies, rats remain in isolation for 4–6 weeks or more (as reviewed by Lapiz et al, 2003; Fone and Porkees, 2008) and are then tested while still in isolation-housed conditions. Thus, rats are tested in a current state of social deprivation in addition to being reared in isolation during post-weaning development (Potegal and Einon, 1989; Hall, 1998).…”

“…In contrast, 5-HT levels and release in the hippocampus appear to be reduced during post-weaning social isolation (with a presumptive compensatory increase in 5-HT 1A receptors), particularly when isolation was initiated in the pre-adolescent period (PD21–28; Table 1). Reduced serotonergic function in the hippocampus may relate to increased anxiety-like behavior observed during and following post-weaning social isolation (Lapiz et al, 2003). Studies of serotonergic activity in the rat amygdala are required following post-weaning social isolation, given that serotonergic activity in the central nucleus of the amygdala (CeA) may relate to heightened anxiety states by promoting behavioral, emotional and endocrine responses to stressors (see Mo et al, 2008).…”