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Pharmacol."],"abstract":"<jats:p>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\u00a0mg\/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\u00a0mg\/kg) and repeated (0.4\u00a0mg\/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\u00a0mg\/kg\/infusion for 10\u00a0days) 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.<\/jats:p>","DOI":"10.3389\/fphar.2022.986566","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T09:16:52Z","timestamp":1662110212000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Nicotine self-administration and ERK signaling are altered in RasGRF2 knockout mice"],"prefix":"10.3389","volume":"13","author":[{"given":"Ilaria","family":"Morella","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronika","family":"Poho\u0159al\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Calpe-L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Brambilla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rainer","family":"Spanagel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rick E.","family":"Bernardi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1111\/acer.12645","article-title":"Alcohol alters the activation of ERK1\/2, a functional regulator of binge alcohol drinking in adult C57BL\/6J mice","volume":"39","author":"Agoglia","year":"2015","journal-title":"Alcohol. 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