Abstract
The central endocannabinoid system (ECS) and the hypothalamic-pituitary-adrenal-axis mediate individual responses to emotionally salient stimuli. Their altered developmental adjustment may relate to the emergence of emotional disturbances. Although environmental influences regulate the individual phenotype throughout the entire lifespan, their effects may result particularly persistent during plastic developmental stages (e.g. prenatal life and adolescence). Here, we investigated whether prenatal stress – in the form of gestational exposure to corticosterone supplemented in the maternal drinking water (100 mg/l) during the last week of pregnancy – combined with a pharmacological stimulation of the ECS during adolescence (daily fatty acid amide hydrolase URB597 i.p. administration - 0.4 mg/kg - between postnatal days 29–38), influenced adult mouse emotional behaviour and brain metabolism measured through in vivo quantitative magnetic resonance spectroscopy. Compared to control mice, URB597-treated subjects showed, in the short-term, reduced locomotion and, in the long term, reduced motivation to execute operant responses to obtain palatable rewards paralleled by reduced levels of inositol and taurine in the prefrontal cortex. Adult mice exposed to prenatal corticosterone showed increased behavioural anxiety and reduced locomotion in the elevated zero maze, and altered brain metabolism (increased glutamate and reduced taurine in the hippocampus; reduced inositol and N-Acetyl-Aspartate in the hypothalamus). Present data further corroborate the view that prenatal stress and pharmacological ECS stimulation during adolescence persistently regulate emotional responses in adulthood. Yet, whilst we hypothesized these factors to be interactive in nature, we observed that the consequences of prenatal corticosterone administration were independent from those of ECS drug-induced stimulation during adolescence.
Highlights
Individual emotional regulations depend on a continuous crosstalk between biological predispositions and environmental challenges [1,2]
The regulatory role exerted by the environment seems to occur primarily during those developmental stages characterized by an elevated degree of phenotypic plasticity, defined as the ‘‘phenotypic modifications that may be expressed by a given organism under contrasting conditions’’ [5,6]
Compared to AFR individuals, PNC adult mice showed increased concentrations of Glu (drug: F(1,23) = 4.64, p = 0.04; prenatal treatment x drug F(1,23) = 0.021, NS) and reduced concentrations of taurine (drug: F(1,23) = 5.992 p = 0.022; prenatal treatment x drug F(1,23) = 0.73, NS). We showed that both prenatal exposure to corticosterone (PNC) and cannabinoid URB597 administration during adolescence significantly modify emotional regulations during development and alter, in the long-term, several indices of brain metabolism
Summary
Individual emotional regulations depend on a continuous crosstalk between biological predispositions and environmental challenges [1,2]. Epidemiological evidence, and clinical and preclinical studies demonstrate that environmental stimulation regulates individual emotional reactivity throughout the entire lifespan [3,4]. A large body of experimental evidence indicates that environmental stress occurring early in life is capable of persistently adjusting emotional regulations between infancy through adulthood [7,8,9]. Just as a series of studies highlight the elevated sensitivity to context characterizing the very early stages of life [1,17], so numerous observations indicate that other developmental phases are characterised by an elevated degree of plasticity Together with influencing individual long-term regulations early in development, external challenges may persistently adjust individual stress and fear reactivity if occurring during adolescence [3]
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