Ryanodine receptor-2 upregulation and nicotine-mediated plasticity.
EMBO J
; 30(1): 194-204, 2011 Jan 05.
Article
em En
| MEDLINE
| ID: mdl-21113126
ABSTRACT
Nicotine, the major psychoactive component of cigarette smoke, modulates neuronal activity to produce Ca2+-dependent changes in gene transcription. However, the downstream targets that underlie the long-term effects of nicotine on neuronal function, and hence behaviour, remain to be elucidated. Here, we demonstrate that nicotine administration to mice upregulates levels of the type 2 ryanodine receptor (RyR2), a Ca2+-release channel present on the endoplasmic reticulum, in a number of brain areas associated with cognition and addiction, notably the cortex and ventral midbrain. Nicotine-mediated RyR2 upregulation was driven by CREB, and caused a long-lasting reinforcement of Ca2+ signalling via the process of Ca2+-induced Ca2+ release. RyR2 upregulation was itself required for long-term phosphorylation of CREB in a positive-feedback signalling loop. We further demonstrate that inhibition of RyR-activation in vivo abolishes sensitization to nicotine-induced habituated locomotion, a well-characterised model for onset of drug dependence. Our findings, therefore, indicate that gene-dependent reprogramming of Ca2+ signalling is involved in nicotine-induced behavioural changes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regulação para Cima
/
Canal de Liberação de Cálcio do Receptor de Rianodina
/
Estimulantes Ganglionares
/
Plasticidade Neuronal
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Nicotina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Reino Unido