{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T15:27:27Z","timestamp":1780759647999,"version":"3.54.1"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T00:00:00Z","timestamp":1584316800000},"content-version":"vor","delay-in-days":75,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1A5A2025272"],"award-info":[{"award-number":["2018R1A5A2025272"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Evidence-Based Complementary and Alternative Medicine"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p>As important components of positive and negative reinforcement, locomotor sensitization and withdrawal anxiety following repeated exposure to nicotine (NIC) constitute crucial risk factors for relapse to NIC use after abstinence. <jats:italic>Glycyrrhiza radix<\/jats:italic> (<jats:italic>G. radix<\/jats:italic>), an important tonic used in traditional Oriental medicine, has not only anxiolytic effects but also reduces NIC\u2010induced locomotor sensitization. Isoliquiritigenin (ISL), a bioactive ingredient of <jats:italic>G. radix<\/jats:italic>, also exhibits neuropharmacological effects, including anxiolytic action. Previously, we reported that ISL suppressed cocaine\u2010induced extracellular dopamine release in the nucleus accumbens shell (NaccSh) and attenuated methamphetamine\u2010induced neurotoxicity. The present study was performed to evaluate the effects of ISL on both NIC withdrawal anxiety and locomotor sensitization. Adult male rats received subcutaneous administration of NIC hydrogen tartrate (0.4\u2009mg\/kg, twice a day) for 7 days followed by 4 days of withdrawal. During the period of NIC withdrawal, the rats received four intragastric treatments with ISL (3, 10, or 30\u2009mg\/kg\/day). All three doses of ISL significantly inhibited NIC withdrawal\u2010induced anxiety\u2010like behaviors in the elevated plus maze (EPM) test, but only the 10\u2009mg\/kg\/day and 30\u2009mg\/kg\/day ISL doses attenuated locomotor sensitization induced by a challenge dose of NIC. Intracerebroventricular ISL also inhibited both NIC\u2010induced withdrawal anxiety and locomotor sensitization, but intra\u2010NaccSh injection of ISL blocked only NIC locomotor sensitization, which was abolished by post\u2010ISL infusion of <jats:italic>tert<\/jats:italic>\u2010butyl hydroperoxide (an oxidant) or <jats:italic>N<\/jats:italic>\u2010methyl\u2010<jats:sc>d<\/jats:sc>\u2010aspartate (NMDA) into the NaccSh. Moreover, there was increased protein expression of phosphorylated Erk1\/2 in the NIC\u2010sensitized NaccSh, which was suppressed by ISL. Taken together, these results suggest that ISL can inhibit repeated NIC\u2010induced withdrawal anxiety and locomotor sensitization, and the latter is mediated by antagonizing accumbal reactive oxygen species and NMDA receptor signaling.<\/jats:p>","DOI":"10.1155\/2020\/9692321","type":"journal-article","created":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T23:31:37Z","timestamp":1584401497000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Isoliquiritigenin Attenuates Anxiety\u2010Like Behavior and Locomotor Sensitization in Rats after Repeated Exposure to Nicotine"],"prefix":"10.1155","volume":"2020","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4516-8486","authenticated-orcid":false,"given":"Yuhua","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0515-0764","authenticated-orcid":false,"given":"Sang 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