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 demonstrate that gene-dependent reprogramming of Ca2+ signalling is involved in nicotine-stimulated neuronal plasticity.
Ryanodine receptor-2 upregulation and nicotine-mediated plasticity / E., Ziviani; Lippi, Giordano; D., Bano; E., Munarriz; Guiducci, Stefania; Zoli, Michele; Kw, Young; P., Nicotera. - In: EMBO JOURNAL. - ISSN 0261-4189. - STAMPA. - 30(2011), pp. 194-204.
Data di pubblicazione: | 2011 |
Titolo: | Ryanodine receptor-2 upregulation and nicotine-mediated plasticity. |
Autore/i: | E., Ziviani; Lippi, Giordano; D., Bano; E., Munarriz; Guiducci, Stefania; Zoli, Michele; Kw, Young; P., Nicotera |
Autore/i UNIMORE: | |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1038/emboj.2010.279 |
Rivista: | |
Volume: | 30 |
Pagina iniziale: | 194 |
Pagina finale: | 204 |
Codice identificativo ISI: | WOS:000287010800018 |
Codice identificativo Scopus: | 2-s2.0-78650911959 |
Codice identificativo Pubmed: | 21113126 |
Citazione: | Ryanodine receptor-2 upregulation and nicotine-mediated plasticity / E., Ziviani; Lippi, Giordano; D., Bano; E., Munarriz; Guiducci, Stefania; Zoli, Michele; Kw, Young; P., Nicotera. - In: EMBO JOURNAL. - ISSN 0261-4189. - STAMPA. - 30(2011), pp. 194-204. |
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