Isoliquiritigenin Attenuates Anxiety-Like Behavior and Locomotor Sensitization in Rats after Repeated Exposure to Nicotine
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. Glycyrrhiza radix (G. radix), an important tonic used in traditional O...
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doaj-daa15bbfb4704094a5b0b115a135bb7a2020-11-25T01:29:03ZengHindawi LimitedEvidence-Based Complementary and Alternative Medicine1741-427X1741-42882020-01-01202010.1155/2020/96923219692321Isoliquiritigenin Attenuates Anxiety-Like Behavior and Locomotor Sensitization in Rats after Repeated Exposure to NicotineYuhua Wang0Sang Chan Kim1Tong Wu2Yu Jiao3Haifeng Jin4Bong Hyo Lee5Chul Won Lee6Yu Fan7Hee Young Kim8Chae Ha Yang9Zhenglin Zhao10Rongjie Zhao11Department of Psychopharmacology, Qiqihar Medical University, Qiqihar 161006, ChinaMedical Research Center, College of Oriental Medicine, Daegu Haany University, Daegu 706-060, Republic of KoreaDepartment of Psychopharmacology, Qiqihar Medical University, Qiqihar 161006, ChinaDepartment of Psychopharmacology, Qiqihar Medical University, Qiqihar 161006, ChinaDepartment of Psychopharmacology, Qiqihar Medical University, Qiqihar 161006, ChinaMedical Research Center, College of Oriental Medicine, Daegu Haany University, Daegu 706-060, Republic of KoreaMedical Research Center, College of Oriental Medicine, Daegu Haany University, Daegu 706-060, Republic of KoreaMedical Research Center, College of Oriental Medicine, Daegu Haany University, Daegu 706-060, Republic of KoreaMedical Research Center, College of Oriental Medicine, Daegu Haany University, Daegu 706-060, Republic of KoreaMedical Research Center, College of Oriental Medicine, Daegu Haany University, Daegu 706-060, Republic of KoreaDepartment of Biochemistry, Qiqihar Medical University, Qiqihar 161006, ChinaDepartment of Psychopharmacology, Qiqihar Medical University, Qiqihar 161006, ChinaAs 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. Glycyrrhiza radix (G. radix), an important tonic used in traditional Oriental medicine, has not only anxiolytic effects but also reduces NIC-induced locomotor sensitization. Isoliquiritigenin (ISL), a bioactive ingredient of G. radix, also exhibits neuropharmacological effects, including anxiolytic action. Previously, we reported that ISL suppressed cocaine-induced extracellular dopamine release in the nucleus accumbens shell (NaccSh) and attenuated methamphetamine-induced 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 mg/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 mg/kg/day). All three doses of ISL significantly inhibited NIC withdrawal-induced anxiety-like behaviors in the elevated plus maze (EPM) test, but only the 10 mg/kg/day and 30 mg/kg/day ISL doses attenuated locomotor sensitization induced by a challenge dose of NIC. Intracerebroventricular ISL also inhibited both NIC-induced withdrawal anxiety and locomotor sensitization, but intra-NaccSh injection of ISL blocked only NIC locomotor sensitization, which was abolished by post-ISL infusion of tert-butyl hydroperoxide (an oxidant) or N-methyl-D-aspartate (NMDA) into the NaccSh. Moreover, there was increased protein expression of phosphorylated Erk1/2 in the NIC-sensitized NaccSh, which was suppressed by ISL. Taken together, these results suggest that ISL can inhibit repeated NIC-induced withdrawal anxiety and locomotor sensitization, and the latter is mediated by antagonizing accumbal reactive oxygen species and NMDA receptor signaling.http://dx.doi.org/10.1155/2020/9692321 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yuhua Wang Sang Chan Kim Tong Wu Yu Jiao Haifeng Jin Bong Hyo Lee Chul Won Lee Yu Fan Hee Young Kim Chae Ha Yang Zhenglin Zhao Rongjie Zhao |
spellingShingle |
Yuhua Wang Sang Chan Kim Tong Wu Yu Jiao Haifeng Jin Bong Hyo Lee Chul Won Lee Yu Fan Hee Young Kim Chae Ha Yang Zhenglin Zhao Rongjie Zhao Isoliquiritigenin Attenuates Anxiety-Like Behavior and Locomotor Sensitization in Rats after Repeated Exposure to Nicotine Evidence-Based Complementary and Alternative Medicine |
author_facet |
Yuhua Wang Sang Chan Kim Tong Wu Yu Jiao Haifeng Jin Bong Hyo Lee Chul Won Lee Yu Fan Hee Young Kim Chae Ha Yang Zhenglin Zhao Rongjie Zhao |
author_sort |
Yuhua Wang |
title |
Isoliquiritigenin Attenuates Anxiety-Like Behavior and Locomotor Sensitization in Rats after Repeated Exposure to Nicotine |
title_short |
Isoliquiritigenin Attenuates Anxiety-Like Behavior and Locomotor Sensitization in Rats after Repeated Exposure to Nicotine |
title_full |
Isoliquiritigenin Attenuates Anxiety-Like Behavior and Locomotor Sensitization in Rats after Repeated Exposure to Nicotine |
title_fullStr |
Isoliquiritigenin Attenuates Anxiety-Like Behavior and Locomotor Sensitization in Rats after Repeated Exposure to Nicotine |
title_full_unstemmed |
Isoliquiritigenin Attenuates Anxiety-Like Behavior and Locomotor Sensitization in Rats after Repeated Exposure to Nicotine |
title_sort |
isoliquiritigenin attenuates anxiety-like behavior and locomotor sensitization in rats after repeated exposure to nicotine |
publisher |
Hindawi Limited |
series |
Evidence-Based Complementary and Alternative Medicine |
issn |
1741-427X 1741-4288 |
publishDate |
2020-01-01 |
description |
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. Glycyrrhiza radix (G. radix), an important tonic used in traditional Oriental medicine, has not only anxiolytic effects but also reduces NIC-induced locomotor sensitization. Isoliquiritigenin (ISL), a bioactive ingredient of G. radix, also exhibits neuropharmacological effects, including anxiolytic action. Previously, we reported that ISL suppressed cocaine-induced extracellular dopamine release in the nucleus accumbens shell (NaccSh) and attenuated methamphetamine-induced 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 mg/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 mg/kg/day). All three doses of ISL significantly inhibited NIC withdrawal-induced anxiety-like behaviors in the elevated plus maze (EPM) test, but only the 10 mg/kg/day and 30 mg/kg/day ISL doses attenuated locomotor sensitization induced by a challenge dose of NIC. Intracerebroventricular ISL also inhibited both NIC-induced withdrawal anxiety and locomotor sensitization, but intra-NaccSh injection of ISL blocked only NIC locomotor sensitization, which was abolished by post-ISL infusion of tert-butyl hydroperoxide (an oxidant) or N-methyl-D-aspartate (NMDA) into the NaccSh. Moreover, there was increased protein expression of phosphorylated Erk1/2 in the NIC-sensitized NaccSh, which was suppressed by ISL. Taken together, these results suggest that ISL can inhibit repeated NIC-induced withdrawal anxiety and locomotor sensitization, and the latter is mediated by antagonizing accumbal reactive oxygen species and NMDA receptor signaling. |
url |
http://dx.doi.org/10.1155/2020/9692321 |
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