Nicotinic receptors mediate stress-nicotine detrimental interplay via dopamine cells' activity.

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 Psychiatry

journal_title

Molecular psychiatry

authors

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 P

doi

10.1038/mp.2017.145

subject

Has Abstract

pub_date

2018-07-01 00:00:00

pages

1597-1605

issue

7

eissn

1359-4184

issn

1476-5578

pii

10.1038/mp.2017.145

journal_volume

23

pub_type

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