Nicotine inhibits the VTA-to-amygdala dopamine pathway to promote anxiety.
Neuron
; 109(16): 2604-2615.e9, 2021 08 18.
Article
in En
| MEDLINE
| ID: mdl-34242565
ABSTRACT
Nicotine stimulates dopamine (DA) neurons of the ventral tegmental area (VTA) to establish and maintain reinforcement. Nicotine also induces anxiety through an as yet unknown circuitry. We found that nicotine injection drives opposite functional responses of two distinct populations of VTA DA neurons with anatomically segregated projections it activates neurons that project to the nucleus accumbens (NAc), whereas it inhibits neurons that project to the amygdala nuclei (Amg). We further show that nicotine mediates anxiety-like behavior by acting on ß2-subunit-containing nicotinic acetylcholine receptors of the VTA. Finally, using optogenetics, we bidirectionally manipulate the VTA-NAc and VTA-Amg pathways to dissociate their contributions to anxiety-like behavior. We show that inhibition of VTA-Amg DA neurons mediates anxiety-like behavior, while their activation prevents the anxiogenic effects of nicotine. These distinct subpopulations of VTA DA neurons with opposite responses to nicotine may differentially drive the anxiogenic and the reinforcing effects of nicotine.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Anxiety
/
Ventral Tegmental Area
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Nicotinic Agonists
/
Neural Pathways
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Nicotine
Limits:
Animals
Language:
En
Journal:
Neuron
Journal subject:
NEUROLOGIA
Year:
2021
Document type:
Article
Affiliation country: