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• W4366273409 endingPage "109548" @default.
• W4366273409 startingPage "109548" @default.
• W4366273409 abstract "Vulnerability to cocaine use disorder depends upon a combination of genetic and environmental risk factors. While early life adversity is a critical environmental vulnerability factor for drug misuse, allelic variants of the monoamine oxidase A (MAOA) gene have been shown to moderate its influence on the risk of drug-related problems. However, data on the interactions between MAOA variants and early life stress (ES) with respect to predisposition to cocaine abuse are limited. Here, we show that a mouse model capturing the interaction of genetic (low-activity alleles of the Maoa gene; MAOANeo) and environmental (i.e., ES) vulnerability factors displays an increased sensitivity to repeated in vivo cocaine psychomotor stimulant actions associated with a reduction of GABAA receptor-mediated inhibition of dopamine neurons of the ventral tegmental area (VTA). Depolarization-induced suppression of inhibition (DSI), a 2-arachidonoylglycerol (2AG)-dependent form of short-term plasticity, also becomes readily expressed by dopamine neurons from male MAOANeo ES mice repeatedly treated with cocaine. The activation of either dopamine D2 or CB1 receptors contributes to cocaine-induced DSI expression, decreased GABA synaptic efficacy, and hyperlocomotion. Next, in vivo pharmacological enhancement of 2AG signaling during repeated cocaine exposure occludes its actions both in vivo and ex vivo. This data extends our knowledge of the multifaceted sequelae imposed by this gene-environment interaction in VTA dopamine neurons of male pre-adolescent mice and contributes to our understanding of neural mechanisms of vulnerability for early onset cocaine use." @default.
• W4366273409 created "2023-04-20" @default.
• W4366273409 creator A5007511127 @default.
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• W4366273409 date "2023-08-01" @default.
• W4366273409 modified "2023-09-27" @default.
• W4366273409 title "Endocannabinoid-dependent decrease of GABAergic transmission on dopaminergic neurons is associated with susceptibility to cocaine stimulant effects in pre-adolescent male MAOA hypomorphic mice exposed to early life stress" @default.
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• W4366273409 doi "https://doi.org/10.1016/j.neuropharm.2023.109548" @default.
• W4366273409 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37080337" @default.
• W4366273409 hasPublicationYear "2023" @default.
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