Abstract
Neonatal handling is an experimental model of early life experience associated with resilience in later life challenges, altering the ability of animals to respond to stress. The endocannabinoid system of the brain modulates the neuroendocrine and behavioral effects of stress, while this system is also capable of being modulated by stress exposure itself. The present study has addressed the question of whether neonatal handling in rats could affect cannabinoid receptors, in an age- and sex-dependent manner, using in situ hybridization and receptor binding techniques. Different effects of neonatal handling were observed in adolescent and adult brain on CB1 receptor mRNA and [3H]CP55,940 binding levels, which in some cases were sexually dimorphic. Neonatal handling interfered in the developmental trajectories of CB1 receptor mRNA levels in striatum and amygdaloid nuclei, as well as of [3H]CP55,940 binding levels in almost all regions studied. Adult handled rats showed reduced [3H]CP55,940 binding levels in the prefrontal cortex, striatum, nucleus accumbens and basolateral amygdala, while binding levels in prefrontal cortex of adolescent handled rats were increased. Finally, handling resulted in decreases in female [3H]CP55,940 binding levels in the striatum, nucleus accumbens, CA3 and DG of dorsal hippocampus and basolateral amygdala. Our results suggest that a brief and repeated maternal separation during the neonatal period induces changes on cannabinoid receptors differently manifested between adolescence and adulthood, male and female brain, which could be correlated to their stress response.
KEYWORDS:
2-AG, 2-arachidonoylglycerol; ANOVA, analysis of variance; Adolescence; BLA, basolateral nucleus of amygdala; BSA, bovine serum albumin; CA1, dorsal field 1 of Ammon’s horn; CA3, dorsal field 3 of Ammon’s horn; CB1 cannabinoid receptors; CB1, cannabinoid receptor 1; CPu-DL, dorsolateral striatum; CPu-VM, ventromedial striatum; CeA, central amygdaloid nucleus; Cg1, anterior cingulate cortex; DG, dentate gyrus; Female rat brain; GR, glucocorticoid receptors; GrDG, dentate gyrus granule cell layer; HPA, hypothalamic-pituitary-adrenal; IL, infralimbic cortex; LTD, long-term depression; MO, medial orbital cortex; Male rat brain; Maternal separation; MoDG, dentate gyrus molecular layer; NAc, nucleus accumbens; NS, not significant; Neonatal handling; PFC, prefrontal cortex; PND, postnatal day; PrL, prelimbic cortex; ROD, relative optical density; RT, room temperature; eCB, endocannabinoid; mPFC, medial prefrontal cortex
- PMID: 30135950
- PMCID: PMC6095101
- DOI: 10.1016/j.ibror.2018.05.002
