RESUMO
RATIONALE: Exposure to early life stress (ELS) is known to have pronounced effects on the prefrontal cortex (PFC). However, not all individuals exposed to ELS manifest the same neurobiological and cognitive phenotypes when adults. Dopamine signaling could be a key factor in understanding the effects of stress on PFC-related cognitive function. OBJECTIVES: We aimed to investigate the differential effects of ELS on cognitive performance of adult mice and the dopaminergic receptors expression in the PFC. METHODS: BALB/c males were exposed to the maternal separation (MS) procedure and their cognitive performance on the eight-arm radial maze (8-RAM) were assessed during adulthood. For molecular-level assessments, we performed mRNA expression analyses for dopamine receptors-DRD1, DRD2, DRD3-and Hers1 expression in the medial PFC. RESULTS: While MS produced an overall impairment on 8-RAM, the stressed animals could be divided in two groups based on their performance: those with impaired cognitive performance (vulnerable to maternal separation, V-MS) and those without any impairment (resilient to maternal separation, R-MS). V-MS animals showed increased DRD1 and DRD2 expression in comparison with other groups. Errors on 8-RAM were also positively correlated with DRD1 and DRD2 mRNA expression. CONCLUSIONS: Our findings suggest a potential role of the dopaminergic system in the programming mechanisms of cognitive vulnerability and resilience related to ELS.
Assuntos
Cognição/fisiologia , Privação Materna , Aprendizagem em Labirinto/fisiologia , Córtex Pré-Frontal/metabolismo , Receptores Dopaminérgicos/metabolismo , Resiliência Psicológica , Animais , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
While increasing evidence posits poor decision-making as a central feature of mental disorders, very few studies investigated the effects of early-life stress (ELS) on specific components of reward-related choice behaviors. Risk-taking (RT) involves the exposure to some danger, or negative consequences, in order to achieve a goal-directed behavior. Such behaviors are likely to be preceded by risk-assessment (RA), which is a dynamic cognitive process involving the acquisition of information in potentially dangerous situations. Here, we investigated the effects of being raised in impoverished housing conditions during early life (P2-P9) on RT, RA and dopaminergic and corticotrophinergic gene expression of adolescent male and female mice. Phenotypes were assessed by two protocols: the elevated plus-maze (EPM) and the predator-odor risk-taking (PORT). We found decreased RA in mice exposed to impoverished housing in the absence of a reward (EPM), with a more pronounced effect among females. Moreover, when exposed to a predatory olfactory cue, increased RT was observed in these females in a reward-related task (PORT), as well as decreased HPA axis responsivity. This sex-specific behavioral effect was associated with increased Crfr1 mRNA expression in the medial prefrontal cortex (mPFC) and higher levels of the histone mark H3R2me2s, a histone modification known to be involved in transcriptional activation, within the promoter of the Crfr1 gene. These findings revealed that ELS exposure can impair the acquisition of environmental information in dangerous situations and increase RT in reward-related scenarios among females, with an important role regarding epigenetic regulation of the Crfr1 gene.