In this study, we evaluated the effects of CBD in modulating the behavioral and neurobiological alterations in a new murine model of FASD, using a PAE paradigm by ethanol gavage administration (3 g/kg/12 h, p.o.) between the gestational day (GD) 7 and PND21 to pregnant females with a previous alcohol consumption history (voluntary ethanol consumption). We found significant emotional (anxiety, depression, and emotional hyperactivity) and cognitive (aversive and spontaneous recognition memories) alterations associated with changes in gene targets correlated with the stress-axis regulation and endocannabinoid system. In addition, a significant reduction in the number of cells, neurofilaments, neuroplasticity, and glutamatergic neurotransmission was found in the hippocampus (HIPP) of PAE-exposed male and female offspring. Changes in specific metabolic pathways in HIPP and prefrontal cortex (PFC) accompanied all these alterations.The results reveal for the first time that CBD’s early and chronic administration normalizes and partially repairs the neuronal damage induced by the FASD model observed at gene, cellular, metabolomic and behavioral levels. Thus, our findings strongly support the potential suitability of CBD in children and young adults with FASD and open opportunities for future clinical trials in this field.
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