Abstract:
:Epidemiological studies report strong association between mood disorders and tobacco addiction. This high comorbidity requires adequate treatment but the underlying mechanisms are unknown. We demonstrate that nicotine exposure, independent of drug withdrawal effects, increases stress sensitivity, a major risk factor in mood disorders. Nicotine and stress concur to induce long-lasting cellular adaptations within the dopamine (DA) system. This interplay is underpinned by marked remodeling of nicotinic systems, causing increased ventral tegmental area (VTA) DA neurons' activity and stress-related behaviors, such as social aversion. Blocking β2 or α7 nicotinic acetylcholine receptors (nAChRs) prevents, respectively, the development and the expression of social stress-induced neuroadaptations; conversely, facilitating α7 nAChRs activation specifically in the VTA promotes stress-induced cellular and behavioral maladaptations. Our work unravels a complex nicotine-stress bidirectional interplay and identifies α7 nAChRs as a promising therapeutic target for stress-related psychiatric disorders.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Morel C,Fernandez SP,Pantouli F,Meye FJ,Marti F,Tolu S,Parnaudeau S,Marie H,Tronche F,Maskos U,Moretti M,Gotti C,Han MH,Bailey A,Mameli M,Barik J,Faure Pdoi
10.1038/mp.2017.145subject
Has Abstractpub_date
2018-07-01 00:00:00pages
1597-1605issue
7eissn
1359-4184issn
1476-5578pii
10.1038/mp.2017.145journal_volume
23pub_type
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