Inoculation stress hypothesis of environmental enrichment

Abstract

One hallmark of psychiatric conditions is the vast continuum of individual differences in susceptibility vs. resilience resulting from the interaction of genetic and environmental factors. The environmental enrichment paradigm is an animal model that is useful for studying a range of psychiatric conditions, including protective phenotypes in addiction and depression models. The major question is how environmental enrichment, a non-drug and non-surgical manipulation, can produce such robust individual differences in such a wide range of behaviors. This paper draws from a variety of published sources to outline a coherent hypothesis of inoculation stress as a factor producing the protective enrichment phenotypes. The basic tenet suggests that chronic mild stress from living in a complex environment and interacting non-aggressively with conspecifics can inoculate enriched rats against subsequent stressors and/or drugs of abuse. This paper reviews the enrichment phenotypes, mulls the fundamental nature of environmental enrichment vs. isolation, discusses the most appropriate control for environmental enrichment, and challenges the idea that cortisol/corticosterone equals stress. The intent of the inoculation stress hypothesis of environmental enrichment is to provide a scaffold with which to build testable hypotheses for the elucidation of the molecular mechanisms underlying these protective phenotypes and thus provide new therapeutic targets to treat psychiatric/neurological conditions.

The effects of extrinsic stress on somatic markers and behavior are dependent on animal housing conditions

“…We found that stress differentially affected behavior depending on the animals' housing background and the specific behavior scrutinized. Altogether, our findings with respect to anxiety and aggression are congruent with the recently postulated inoculation stress hypothesis [39]. This hypothesis claims that particular chronic mild stress, such as stress that originates from living in a complex social environment, can protect against subsequent stressors.…”

“…Environmental enrichment has been suggested to be the functional inverse of stress [38] but SEEs can simultaneously parallel the endocrine, neurobiological, behavioral and physiological aspects of stress [39]. Thus, it is not clear whether SEEs would intensify the effects of stress on behavior or whether this type of housing would buffer the effects of external stressors.…”

Combining the Antipsychotic Drug Haloperidol and Environmental Enrichment after Traumatic Brain Injury Is a Double-Edged Sword

“…61 The protective effects of EE may also partially result from the inoculation stress hypothesis, put forth by Crofton and colleagues (2015), which briefly posits that mild stress associated with living in a complex setting and interacting with conspecifics in a non-aggressive manner "inoculates" the rats against consequent stressors and/or drugs of abuse. 62 This theory could certainly be extrapolated to explain the EE-related attenuation of HAL-induced detrimental effects observed in the current study.…”

Adolescent environmental enrichment prevents behavioral and physiological sequelae of adolescent chronic stress in female (but not male) rats

“…According to the match/ mismatch hypothesis and inoculation stress hypotheses, early life enrichment may serve as a mild stressor that causes biological adaptations to optimally prepare, or “inoculate” the organism for coping with subsequent stress exposure (Crofton, Zhang, & Green, 2015, Schmidt, 2011). Future studies are required to examine whether enrichment and/or concurrent stress and enrichment can block or attenuate chronic stress-related behavioral disruptions later in life.…”