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

• Verfasst von: Morella, Ilaria [VerfasserIn]
• Verfasst von: Pohořalá, Veronika [VerfasserIn]
• Verfasst von: Calpe-López, Claudia [VerfasserIn]
• Verfasst von: Brambilla, Riccardo [VerfasserIn]
• Verfasst von: Spanagel, Rainer [VerfasserIn]
• Verfasst von: Bernardi, Rick E. [VerfasserIn]
• Titel: Nicotine self-administration and ERK signaling are altered in RasGRF2 knockout mice
• Verf.angabe: Ilaria Morella, Veronika Pohořalá, Claudia Calpe-López, Riccardo Brambilla, Rainer Spanagel and Rick E. Bernardi
• E-Jahr: 2022
• Jahr: 02 September 2022
• Umfang: 10 S.
• Fussnoten: Gesehen am 02.10.2023
• Titel Quelle: Enthalten in: Frontiers in pharmacology
• Ort Quelle: Lausanne : Frontiers Media, 2010
• Jahr Quelle: 2022
• Band/Heft Quelle: 13(2022), Artikel-ID 986566, Seite 1-10
• ISSN Quelle: 1663-9812
• DOI: doi:10.3389/fphar.2022.986566
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1860568947

Abstract

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.