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- W4376602271 endingPage "1820" @default.
- W4376602271 startingPage "1808" @default.
- W4376602271 abstract "Fetal alcohol exposure has deleterious consequences on the motor skills of patients affected by Fetal Alcohol Spectrum Disorder (FASD) and in pre-clinical models of gestational ethanol exposure (GEE). Deficits in striatal cholinergic interneurons (CINs) and dopamine function impair action learning and execution, yet the effects of GEE on acetylcholine (ACh) and striatal dopamine release remain unexplored. Here, we report that alcohol exposure during the first ten postnatal days (GEEP0-P10), which mimics ethanol consumption during the last gestational trimester in humans, induces sex-specific anatomical and motor skill deficits in female mice during adulthood. Consistent with these behavioral impairments, we observed increased stimulus evoked-dopamine levels in the dorsolateral striatum (DLS) of GEEP0-P10 female, but not male, mice. Further experiments revealed sex-specific deficits in β2-containing nicotinic ACh receptor (nAChR)-modulation of electrically evoked dopamine release. Moreover, we found a reduced decay of ACh transients and a decreased excitability of striatal CINs in DLS of GEEP0-P10 females, indicating striatal CIN dysfunctions. Finally, the administration of varenicline, a β2-containing nAChR partial agonist, and chemogenetic-mediated increase in CIN activity improved motor performance in adult GEEP0-P10 females. Altogether, these data shed new light on GEE-induced striatal deficits and establish potential pharmacological and circuit-specific interventions to ameliorate motor symptoms of FASD." @default.
- W4376602271 created "2023-05-17" @default.
- W4376602271 creator A5028546529 @default.
- W4376602271 creator A5059434070 @default.
- W4376602271 creator A5061918050 @default.
- W4376602271 creator A5090525570 @default.
- W4376602271 date "2023-05-15" @default.
- W4376602271 modified "2023-10-18" @default.
- W4376602271 title "Gestational ethanol exposure impairs motor skills in female mice through dysregulated striatal dopamine and acetylcholine function" @default.
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- W4376602271 doi "https://doi.org/10.1038/s41386-023-01594-4" @default.
- W4376602271 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37188849" @default.
- W4376602271 hasPublicationYear "2023" @default.