Neural circuits and nicotinic acetylcholine receptors mediate the cholinergic regulation of midbrain dopaminergic neurons and nicotine dependence.
Acta Pharmacol Sin
; 41(1): 1-9, 2020 Jan.
Article
en En
| MEDLINE
| ID: mdl-31554960
ABSTRACT
Midbrain dopaminergic (DA) neurons are governed by an endogenous cholinergic system, originated in the mesopontine nuclei. Nicotine hijacks nicotinic acetylcholine receptors (nAChRs) and interferes with physiological function of the cholinergic system. In this review, we describe the anatomical organization of the cholinergic system and the key nAChR subtypes mediating cholinergic regulation of DA transmission and nicotine reward and dependence, in an effort to identify potential targets for smoking intervention. Cholinergic modulation of midbrain DA systems relies on topographic organization of mesopontine cholinergic projections, and activation of nAChRs in midbrain DA neurons. Previous studies have revealed that α4, α6, and ß2 subunit-containing nAChRs expressed in midbrain DA neurons and their terminals in the striatum regulate firings of midbrain DA neurons and activity-dependent dopamine release in the striatum. These nAChRs undergo modification upon chronic nicotine exposure. Clinical investigation has demonstrated that partial agonists of these receptors elevate the success rate of smoking cessation relative to placebo. However, further investigations are required to refine the drug targets to mitigate unpleasant side-effects.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Tabaquismo
/
Mesencéfalo
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Receptores Nicotínicos
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Neuronas Colinérgicas
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Neuronas Dopaminérgicas
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Vías Nerviosas
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Nicotina
Tipo de estudio:
Clinical_trials
Límite:
Animals
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Humans
Idioma:
En
Revista:
Acta Pharmacol Sin
Asunto de la revista:
FARMACOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China