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We recently reported that the expression of fibroblast growth factor 2 (<jats:italic>Fgf2<\/jats:italic>) is increased in the striatum of rodents following long\u2010term excessive alcohol drinking and that the systemic or intra\u2010striatal administration of recombinant FGF2 increases alcohol consumption. Here, we set out to determine whether the endogenous FGF2 plays a role in alcohol drinking and reward, by testing the behavioural phenotype of <jats:italic>Fgf2<\/jats:italic> knockout mice. We found that <jats:italic>Fgf2<\/jats:italic> deficiency resulted in decreased alcohol consumption when tested in two\u2010bottle choice procedures with various alcohol concentrations. Importantly, these effects were specific for alcohol, as a natural reward (sucrose) or water consumption was not affected by <jats:italic>Fgf2<\/jats:italic> deficiency. In addition, <jats:italic>Fgf2<\/jats:italic> knockout mice failed to show alcohol\u2010conditioned place preference (CPP) but showed normal fear conditioning, suggesting that deletion of the growth factor reduces alcohol's rewarding properties. Finally, <jats:italic>Fgf2<\/jats:italic> knockout mice took longer to recover from the loss of righting reflex and showed higher blood alcohol concentrations when challenged with an intoxicating alcohol dose, suggesting that their ethanol metabolism might be affected. Together, our results show that the endogenous FGF2 plays a critical role in alcohol drinking and reward and indicate that FGF2 is a positive regulator of alcohol\u2010drinking behaviours. Our findings suggest that FGF2 is a potential biomarker for problem alcohol drinking and is a potential target for pharmacotherapy development for AUD.<\/jats:p>","DOI":"10.1111\/adb.13115","type":"journal-article","created":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T05:41:37Z","timestamp":1637300497000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["FGF2 is an endogenous regulator of alcohol reward and consumption"],"prefix":"10.1111","volume":"27","author":[{"given":"Oren","family":"Even\u2010Chen","sequence":"first","affiliation":[{"name":"School of Psychological Sciences Tel Aviv University  Tel Aviv 69978 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie","family":"Herburg","sequence":"additional","affiliation":[{"name":"Institute of Neuroanatomy and Cell Biology Hannover Medical School  Carl\u2010Neuberg\u2010Stra\u00dfe 1 Hanover 30625 Germany"},{"name":"Center for Systems Neuroscience (ZSN)  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterini","family":"Kefalakes","sequence":"additional","affiliation":[{"name":"Institute of Neuroanatomy and Cell Biology Hannover Medical School  Carl\u2010Neuberg\u2010Stra\u00dfe 1 Hanover 30625 Germany"},{"name":"Center for Systems Neuroscience (ZSN)  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nataly","family":"Urshansky","sequence":"additional","affiliation":[{"name":"School of Psychological Sciences Tel Aviv University  Tel Aviv 69978 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Grothe","sequence":"additional","affiliation":[{"name":"Institute of Neuroanatomy and Cell Biology Hannover Medical School  Carl\u2010Neuberg\u2010Stra\u00dfe 1 Hanover 30625 Germany"},{"name":"Center for Systems Neuroscience (ZSN)  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3143-6777","authenticated-orcid":false,"given":"Segev","family":"Barak","sequence":"additional","affiliation":[{"name":"School of Psychological Sciences Tel Aviv University  Tel Aviv 69978 Israel"},{"name":"Sagol School of Neuroscience Tel Aviv University  Tel Aviv 69978 Israel"},{"name":"Department of Neurobiology, The George S. 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