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

Morella, Ilaria ORCID:, Pohořalá, Veronika, Calpe-López, Claudia, Brambilla, Riccardo ORCID:, Spanagel, Rainer and Bernardi, Rick E. 2022. Nicotine self-administration and ERK signaling are altered in RasGRF2 knockout mice. Frontiers in Pharmacology 13 , 986566. 10.3389/fphar.2022.986566

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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 Type: Article
Date Type: Published Online
Status: Published
Schools: Biosciences
Neuroscience and Mental Health Research Institute (NMHRI)
Additional Information: License information from Publisher: LICENSE 1: URL:
Publisher: Frontiers Media
Date of First Compliant Deposit: 20 September 2022
Date of Acceptance: 10 August 2022
Last Modified: 23 May 2023 14:19

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