Abstract
Environmental enrichment produces protective addiction and depression phenotypes in rats. ΔFosB is a transcription factor that regulates reward in the brain and is induced by psychological stress as well as drugs of abuse. However, the role played by ΔFosB in the protective phenotypes of environmental enrichment has not been well studied. Here, we demonstrate that ΔFosB is differentially regulated in rats reared in an isolated condition (IC) compared to those in an enriched condition (EC) in response to restraint stress or cocaine. Chronic stress or chronic cocaine treatment each elevates ΔFosB protein levels in the nucleus accumbens (NAc) of IC rats, but not of EC rats due to an already elevated basal accumulation of ΔFosB seen under EC conditions. Viral-mediated overexpression of ΔFosB in the NAc shell of pair-housed rats (i.e., independent of environmental enrichment/isolation) increases operant responding for sucrose when motivated by hunger, but decreases responding in satiated animals. Moreover, ΔFosB overexpression decreases cocaine self-administration, enhances extinction of cocaine seeking, and decreases cocaine-induced reinstatement of intravenous cocaine self-administration; all behavioral findings consistent with the enrichment phenotype. In contrast, however, ΔFosB overexpression did not alter responses of pair-housed rats in several tests of anxiety- and depression-related behavior. Thus, ΔFosB in the NAc the shell mimics the protective addiction phenotype, but not the protective depression phenotype of environmental enrichment.
Highlights
Life experience, especially in the early stages of life, has a profound impact on the behavior of animals throughout life
The interaction was such that, after repeated restraint stress, the number of ∆FosB positive cells significantly increased in isolated condition (IC) rats, while this number did not change in enriched condition (EC) rats after repeated stress
Environmental enrichment is a paradigm that manipulates the living environment of animals, producing protective effects against many psychiatric conditions. ∆FosB plays a key role in regulating reward function in multiple brain regions, including the nucleus accumbens (NAc) and dorsal striatum (Koob et al, 1998; Wise, 1998; Wallace et al, 2008; Grueter et al, 2013; Pitchers et al, 2013)
Summary
Especially in the early stages of life, has a profound impact on the behavior of animals throughout life. In rodent models, living in an enriched environment from weaning through young adulthood was reported to produce protective addiction and depression phenotypes (Green et al, 2002, 2003, 2010; Laviola et al, 2008; Solinas et al, 2008, 2009; El Rawas et al, 2009; Thiel et al, 2009, 2010) In this paradigm, animals are assigned to either an enriched condition (EC) in which animals are group-housed and have daily access to novel objects, or an isolated condition (IC) in which animals are single housed without novelty or social contact. This approach is the environmental equivalent to well established genetic strategies such as selective breeding (McBride et al, 2014)
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