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Nicotine self-administration and ERK signaling are altered in RasGRF2 knockout mice

Ras/Raf/MEK/ERK (Ras-ERK) signaling has been demonstrated to play a role in the effects of drugs of abuse such as cocaine and alcohol, but has not been extensively examined in nicotine-related reward behaviors. We examined the role of Ras Guanine Nucleotide Releasing Factor 2 (RasGRF2), an upstream...

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Main Authors: Morella, Ilaria (Author) , Pohořalá, Veronika (Author) , Calpe-López, Claudia (Author) , Brambilla, Riccardo (Author) , Spanagel, Rainer (Author) , Bernardi, Rick E. (Author)
Format: Article (Journal)
Language:English
Published: 02 September 2022
In: Frontiers in pharmacology
Year: 2022, Volume: 13, Pages: 1-10
ISSN:1663-9812
DOI:10.3389/fphar.2022.986566
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.3389/fphar.2022.986566
Verlag, kostenfrei, Volltext: https://www.frontiersin.org/articles/10.3389/fphar.2022.986566
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Author Notes:Ilaria Morella, Veronika Pohořalá, Claudia Calpe-López, Riccardo Brambilla, Rainer Spanagel and Rick E. Bernardi
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Summary:Ras/Raf/MEK/ERK (Ras-ERK) signaling has been demonstrated to play a role in the effects of drugs of abuse such as cocaine and alcohol, but has not been extensively examined in nicotine-related reward behaviors. We examined the role of Ras Guanine Nucleotide Releasing Factor 2 (RasGRF2), an upstream mediator of the Ras-ERK signaling pathway, on nicotine self-administration (SA) in RasGRF2 KO and WT mice. We first demonstrated that acute nicotine exposure (0.4 mg/kg) resulted in an increase in phosphorylated ERK1/2 (pERK1/2) in the striatum, consistent with previous reports. We also demonstrated that increases in pERK1/2 resulting from acute (0.4 mg/kg) and repeated (0.4 mg/kg, 10 daily injections) exposure to nicotine in WT mice were not present in RasGRF2 KO mice, confirming that RasGRF2 at least partly regulates the activity of the Ras-ERK signaling pathway following nicotine exposure. We then performed intravenous nicotine SA (0.03 mg/kg/infusion for 10 days) in RasGRF2 KO and WT mice. Consistent with a previous report using cocaine SA, RasGRF2 KO mice demonstrated an increase in nicotine SA relative to WT controls. These findings suggest a role for RasGRF2 in the reinforcing effects of nicotine, and implicate the Ras-ERK signaling pathway as a common mediator of the response to drugs of abuse.
Item Description:Gesehen am 02.10.2023
Physical Description:Online Resource
ISSN:1663-9812
DOI:10.3389/fphar.2022.986566

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