Effects of an early life experience on rat brain cannabinoid receptors in adolescence and adulthood

Vangopoulou, Chara; Bourmpoula, Maria; Koupourtidou, Christina; Giompres, Panagiotis; Stamatakis, Antonios; Kouvelas, Elias D.; Mitsacos, Ada

doi:10.1016/j.ibror.2018.05.002

Cited by 18 publications

(10 citation statements)

References 112 publications

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“…In situ hybridization was performed as previously described (Vangopoulou et al, 2018). Frozen sections were let to thaw at RT, postfixed in 4%paraformaldehyde in phosphate-buffered saline (0.1 M PBS; pH 7.4, containing 0.1% diethylpyrocarbonate) for 5 min, and washed in PBS for 3 min.…”

Section: Brain Dissection and In Situ Hybridizationmentioning

confidence: 99%

Neonatal maternal separation affects metabotropic glutamate receptor 5 expression and anxiety‐related behavior of adult rats

Tsotsokou

Νικολακοπούλου

Kouvelas

et al. 2021

Eur J of Neuroscience

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Exposure to early life stress leads to long-term neurochemical and behavioral alterations. Stress-induced psychiatric disorders, such as depression, have recently been linked to dysregulation of glutamate signaling, mainly via its postsynaptic receptors. The role of metabotropic glutamate receptor 5 (mGluR5) in stress-induced psychopathology has been the target of several studies in humans. In rodents, blockade of mGluR5 produces antidepressantlike actions, whereas mice lacking mGluR5 exhibit altered anxiety-like behaviors and learning. In this study, we used well-known rodent models of early life stress based on mother-infant separation during the first 3 weeks of life in order to examine the effects of neonatal maternal separation on mGluR5 expression and on anxiety-related behavior in adulthood. We observed that brief (15 min) neonatal maternal separation, but not prolonged (3 h), induced increases in mGluR5 mRNA and protein expression levels in medial prefrontal cortex and mGluR5 protein levels in dorsal, but not ventral, hippocampus of adult rat brain. Behavioral testing using the open-field and the elevated-plus maze tasks showed that brief maternal separations resulted in increased exploratory and decreased anxiety-related behavior, whereas prolonged maternal separations resulted in increased anxiety-related behavior in adulthood. The data indicate that the long-lasting effects of neonatal mother-offspring separation on anxiety-like behavior and mGluR5 expression depend on the duration of maternal separation and suggest that the increased mGluR5 receptors in medial prefrontal cortex and hippocampus of adult rats exposed to brief neonatal maternal separations may underlie their heightened ability to cope with stress.

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Section: Brain Dissection and In Situ Hybridizationmentioning

confidence: 99%

Neonatal maternal separation affects metabotropic glutamate receptor 5 expression and anxiety‐related behavior of adult rats

Tsotsokou

Νικολακοπούλου

Kouvelas

et al. 2021

Eur J of Neuroscience

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“…The ECS also plays a specific role in neural development, controlling the establishment of cortical–subcortical connections especially by densities of its receptors in the corticolimbic system (Belue, Howlett, Westlake, & Hutchings, 1995; de Fonseca, Ramos, Bonnin, & Fernández‐Ruiz, 1993; Mato, Olmo, & Pazos, 2003). In addition, there are many reports supporting ECS regulation of stress responsivity and emotional behavior from young to old ages; thus, this system is a promising therapeutic target for anxiety‐ and stress‐related disorders (Hillard, Beatka, & Sarvaideo, 2016; Katzman, Furtado, & Anand, 2016; Micale & Drago, 2018; Patel, Hill, Cheer, Wotjak, & Holmes, 2017; Vangopoulou et al, 2018; Wyrofsky et al, 2019).…”

Section: The Endocannabinoid Systemmentioning

confidence: 99%

Early life stress and development of the endocannabinoid system: A bidirectional process in programming future coping

Ferber

Trezza

Weller

2019

Developmental Psychobiology

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The endocannabinoid system (ECS) critically regulates stress responsivity and emotional behavior throughout development. It regulates anxiety‐like behaviors in humans and animal models. In addition, it is sensitive to early life stress at the gene expression level in a sex‐dependent and region‐dependent manner, and these changes are already evident in the adolescent brain. The ECS modulates the neuroendocrine and behavioral effects of stress, and is also capable of being affected by stress exposure itself. Early life stress interferes with the development of corticolimbic circuits, a major location of endocannabinoid receptors, and increases vulnerability to adult psychopathology. Early life stress alters the ontogeny of the ECS, resulting in a sustained deficit in its function, particularly within the hippocampus. Specifically, exposure to early stress results in bidirectional changes in anandamide and 2‐AG tissue levels within the amygdala and hippocampus and reduces hippocampal endocannabinoid function at puberty. CB1 receptor densities across all brain regions are downregulated later in life following exposure to early life stress. Manipulations affecting the glucocorticoid and the endocannabinoid systems persistently adjust individual emotional responses and synaptic plasticity. This review aims to show the bidirectional trajectories of endocannabinoid modulation of emotionality in reaction to early life stress.

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“…These sex differences in the cannabinoid system may be important for key sex differences observed in behavior following stressors. Early-life stress affects the endocannabinoid system by (a) decreasing CB1Rs in adulthood in males 27 across various cortical regions as concluded through [ 3 H]CP55,940 binding and mRNA expression, though findings in females have been mixed 28 , and (b) increasing gene expression for endocannabinoid degradation enzymes 29 , though surprisingly these effects have not been studied in the cerebellum. Although endocannabinoids have not been thoroughly investigated in the cerebellum, males have been shown to exhibit increased cerebellar 2-AG compared to females 30 .…”

Section: Endocannabinoid Regulation Of Stressmentioning

confidence: 99%

Long-term aberrations to cerebellar endocannabinoids induced by early-life stress

Moussa-Tooks

Larson

Gimeno

et al. 2019

Preprint

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AbstractStudies of early-life stress traditionally focus on glucocorticoid signaling as a modulator of neurodevelopmental risk, but emerging evidence points to the role of the endocannabinoid system in long-term stress-induced neural remodeling. Existing studies on stress-induced endocannabinoid dysregulation have focused on changes to cerebrum that are temporally proximal to stressors, but little is known about temporally distal effects, especially in cerebellum, which is vulnerable to early developmental stress and is dense with cannabinoid receptors. Further, sex-specific effects of stress on cerebellar endocannabinoid tone are understudied. Following a naturalistic rodent model of early-life stress, limited bedding at postnatal days 2-9, adult (postnatal day 70) cerebellar and hippocampal endocannabinoids and related lipids and mRNA were assessed, and behavioral performance was evaluated. Regional and sex-specific effects were present at baseline and following early-life stress. Limited bedding impaired peripherally-measured basal corticosterone in adult males only. In the CNS, early-life stress (1) decreased 2-arachidonoyl glycerol and arachidonic acid in the cerebellar deep nuclei in males only; (2) decreased 2-arachidonoyl glycerol in females only in cerebellar Crus I; and (3) increased dorsal hippocampus prostaglandins in males only. Transcriptomics for cerebellar interpositus nucleus revealed substantial sex effects, with minimal effects of stress. Stress did impair novel object recognition in both sexes and social preference in females. Taken together, the cerebellar endocannabinoids system exhibits robust sex-specific differences, malleable through early-life stress and perhaps also contributing to sexual differentiation of the brain. The current study may foster future research into stress as a risk factor for cerebellar-related dysfunctions.

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Effects of an early life experience on rat brain cannabinoid receptors in adolescence and adulthood

Cited by 18 publications

References 112 publications

Neonatal maternal separation affects metabotropic glutamate receptor 5 expression and anxiety‐related behavior of adult rats

Neonatal maternal separation affects metabotropic glutamate receptor 5 expression and anxiety‐related behavior of adult rats

Early life stress and development of the endocannabinoid system: A bidirectional process in programming future coping

Long-term aberrations to cerebellar endocannabinoids induced by early-life stress

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