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(Fabaceae; licorice) is a widely used medicinal herb known to exert protective effects against multiple neurological diseases. The flavonoid, isoliquiritigenin (ISL), is a main constituent of roots of\n                      <jats:italic>Glycyrrhiza glabra<\/jats:italic>\n                      . ISL has been reported to behave as a GABA\n                      <jats:sub>B<\/jats:sub>\n                      receptor agonist and exert multiple pharmacological effects. Given the role of the GABA\n                      <jats:sub>B<\/jats:sub>\n                      receptor in the neurobiological and pharmacological bases of alcohol use disorder, the present study investigated the effect of ISL on a series of alcohol-related behaviors in selectively bred, female Sardinian alcohol-preferring rats.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      The collected results indicated that acute treatment with ISL (5-20 mg\/kg, i.p.; 50-200 mg\/kg, i.g.) decreased operant oral alcohol self-administration under both fixed and progressive ratio schedules of reinforcement and suppressed cue-induced reinstatement of alcohol seeking. ISL effect on alcohol self-administration was partially blocked by pretreatment with the GABA\n                      <jats:sub>B<\/jats:sub>\n                      receptor antagonist, SCH50911, and potentiated by co-administration of the positive allosteric modulator of the GABA\n                      <jats:sub>B<\/jats:sub>\n                      receptor, GS39783. Acute treatment with doses of ISL as high as 80 mg\/kg (i.p.) did not alter spontaneous locomotor activity, suggestive of the specificity of ISL effects on alcohol-related behaviors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These results confirm the ability of ISL to behave\n                      <jats:italic>in vivo<\/jats:italic>\n                      as a GABA\n                      <jats:sub>B<\/jats:sub>\n                      receptor agonist; they also indicate that ISL reproduced the suppressing effects of the prototypic GABA\n                      <jats:sub>B<\/jats:sub>\n                      receptor agonist, baclofen, on multiple alcohol-related behaviors in rodents.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00213-025-06892-x","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T01:33:17Z","timestamp":1758591197000},"page":"1151-1169","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Reducing effects of isoliquiritigenin, a naturally occurring GABAB receptor agonist, on alcohol-motivated behaviors in alcohol-preferring rats"],"prefix":"10.1007","volume":"243","author":[{"given":"Paola","family":"Maccioni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Regonini Somenzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro A. 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