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Different development patterns of reward behaviors induced by ketamine and JWH-018 in striatal GAD67 knockdown mice
Glutamic acid decarboxylase 67 (GAD67) is a gamma-aminobutyric acid (GABA) synthesis enzyme associated with the function of other neurotransmitter receptors, such as the N-methyl-D-aspartate (NMDA) receptor and cannabinoid receptor 1. However, the role of GAD67 in the development of different abused...
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Published in: | Journal of veterinary science (Suwŏn-si, Korea) 2024, 25(5), , pp.0-0 |
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container_title | Journal of veterinary science (Suwŏn-si, Korea) |
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creator | Gu, Sun Mi Hong, Eunchong Seo, Sowoon Kim, Sanghyeon Yoon, Seong Shoon Cha, Hye Jin Yun, Jaesuk |
description | Glutamic acid decarboxylase 67 (GAD67) is a gamma-aminobutyric acid (GABA) synthesis enzyme associated with the function of other neurotransmitter receptors, such as the N-methyl-D-aspartate (NMDA) receptor and cannabinoid receptor 1. However, the role of GAD67 in the development of different abused drug-induced reward behaviors remains unknown. In order to elucidate the mechanisms of substance use disorder, it is crucial to study changes in biomarkers within the brain's reward circuit induced by drug use.
The study was designed to examine the effects of the downregulation of GAD67 expression in the dorsal striatum on reward behavior development.
We evaluated the effects of GAD67 knockdown on depression-like behavior and anxiety using the forced swim test and elevated plus maze test in a mouse model. We further determined the effects of GAD67 knockdown on ketamine- and JWH-018-induced conditioned place preference (CPP).
Knockdown of GAD67 in the dorsal striatum of mice increased depression-like behavior, but it decreased anxiety. Moreover, the CPP score on the NMDA receptor antagonist ketamine was increased by GAD67 knockdown, whereas the administration of JWH-018, a cannabinoid receptor agonist, did not affect the CPP score in the GAD67 knockdown mice group compared with the control group.
These results suggest that striatal GAD67 reduces GABAergic neuronal activity and may cause ketamine-induced NMDA receptor inhibition. Consequently, GAD67 downregulation induces vulnerability to the drug reward behavior of ketamine. |
doi_str_mv | 10.4142/jvs.23325 |
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The study was designed to examine the effects of the downregulation of GAD67 expression in the dorsal striatum on reward behavior development.
We evaluated the effects of GAD67 knockdown on depression-like behavior and anxiety using the forced swim test and elevated plus maze test in a mouse model. We further determined the effects of GAD67 knockdown on ketamine- and JWH-018-induced conditioned place preference (CPP).
Knockdown of GAD67 in the dorsal striatum of mice increased depression-like behavior, but it decreased anxiety. Moreover, the CPP score on the NMDA receptor antagonist ketamine was increased by GAD67 knockdown, whereas the administration of JWH-018, a cannabinoid receptor agonist, did not affect the CPP score in the GAD67 knockdown mice group compared with the control group.
These results suggest that striatal GAD67 reduces GABAergic neuronal activity and may cause ketamine-induced NMDA receptor inhibition. Consequently, GAD67 downregulation induces vulnerability to the drug reward behavior of ketamine.</description><identifier>ISSN: 1229-845X</identifier><identifier>ISSN: 1976-555X</identifier><identifier>EISSN: 1976-555X</identifier><identifier>DOI: 10.4142/jvs.23325</identifier><identifier>PMID: 39231788</identifier><language>eng</language><publisher>Korea (South): The Korean Society of Veterinary Science</publisher><subject>Animals ; Anxiety ; Corpus Striatum - drug effects ; Corpus Striatum - metabolism ; Depression - chemically induced ; Gene Knockdown Techniques ; Glutamate Decarboxylase - genetics ; Glutamate Decarboxylase - metabolism ; Indoles - pharmacology ; Ketamine - pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Naphthalenes - pharmacology ; Research Report ; Reward ; 수의학</subject><ispartof>Journal of Veterinary Science, 2024, 25(5), , pp.0-0</ispartof><rights>2024 The Korean Society of Veterinary Science.</rights><rights>2024 The Korean Society of Veterinary Science 2024 The Korean Society of Veterinary Science</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c301t-9271f07ba0451224e31220e4df2c4f9169861e3e38091f23ed37da979d5538263</cites><orcidid>0000-0002-3093-8919 ; 0000-0002-7907-0487 ; 0009-0007-4882-6492 ; 0009-0006-8239-9570 ; 0009-0003-8823-3035 ; 0000-0002-8182-1024 ; 0009-0002-9523-0759</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11450393/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11450393/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39231788$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.kci.go.kr/kciportal/ci/sereArticleSearch/ciSereArtiView.kci?sereArticleSearchBean.artiId=ART003123871$$DAccess content in National Research Foundation of Korea (NRF)$$Hfree_for_read</backlink></links><search><creatorcontrib>Gu, Sun Mi</creatorcontrib><creatorcontrib>Hong, Eunchong</creatorcontrib><creatorcontrib>Seo, Sowoon</creatorcontrib><creatorcontrib>Kim, Sanghyeon</creatorcontrib><creatorcontrib>Yoon, Seong Shoon</creatorcontrib><creatorcontrib>Cha, Hye Jin</creatorcontrib><creatorcontrib>Yun, Jaesuk</creatorcontrib><title>Different development patterns of reward behaviors induced by ketamine and JWH-018 in striatal GAD67 knockdown mice</title><title>Journal of veterinary science (Suwŏn-si, Korea)</title><addtitle>J Vet Sci</addtitle><description>Glutamic acid decarboxylase 67 (GAD67) is a gamma-aminobutyric acid (GABA) synthesis enzyme associated with the function of other neurotransmitter receptors, such as the N-methyl-D-aspartate (NMDA) receptor and cannabinoid receptor 1. However, the role of GAD67 in the development of different abused drug-induced reward behaviors remains unknown. In order to elucidate the mechanisms of substance use disorder, it is crucial to study changes in biomarkers within the brain's reward circuit induced by drug use.
The study was designed to examine the effects of the downregulation of GAD67 expression in the dorsal striatum on reward behavior development.
We evaluated the effects of GAD67 knockdown on depression-like behavior and anxiety using the forced swim test and elevated plus maze test in a mouse model. We further determined the effects of GAD67 knockdown on ketamine- and JWH-018-induced conditioned place preference (CPP).
Knockdown of GAD67 in the dorsal striatum of mice increased depression-like behavior, but it decreased anxiety. Moreover, the CPP score on the NMDA receptor antagonist ketamine was increased by GAD67 knockdown, whereas the administration of JWH-018, a cannabinoid receptor agonist, did not affect the CPP score in the GAD67 knockdown mice group compared with the control group.
These results suggest that striatal GAD67 reduces GABAergic neuronal activity and may cause ketamine-induced NMDA receptor inhibition. Consequently, GAD67 downregulation induces vulnerability to the drug reward behavior of ketamine.</description><subject>Animals</subject><subject>Anxiety</subject><subject>Corpus Striatum - drug effects</subject><subject>Corpus Striatum - metabolism</subject><subject>Depression - chemically induced</subject><subject>Gene Knockdown Techniques</subject><subject>Glutamate Decarboxylase - genetics</subject><subject>Glutamate Decarboxylase - metabolism</subject><subject>Indoles - pharmacology</subject><subject>Ketamine - pharmacology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Naphthalenes - pharmacology</subject><subject>Research Report</subject><subject>Reward</subject><subject>수의학</subject><issn>1229-845X</issn><issn>1976-555X</issn><issn>1976-555X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNpVkU1v1DAQhi0EoqVw4A8gHwEpxZ9JfEKrln6gSkioiN4srz2mbhJ7a2e36r-vu1squHhGnsfvzPhF6D0lh4IK9uVmUw4Z50y-QPtUdW0jpbx6WXPGVNMLebWH3pRyQ0hFWvUa7XHFOO36fh-V4-A9ZIgzdrCBMa2mx3xl5hlyLDh5nOHOZIeXcG02IeWCQ3RrC_XmHg8wmylEwCY6_P33WUNoX-u4zDmY2Yz4dHHcdniIyQ4u3UU8BQtv0StvxgLvnuIB-nXy7fLorLn4cXp-tLhoLCd0bhTrqCfd0hAh6yYCeD0JCOeZFV7RVvUtBQ68J4p6xsHxzhnVKScl71nLD9DnnW7MXg826GTCNv5Jesh68fPyXFPSMtESUeGvO3i1Xk7gbP2FbEa9ymEy-X779P9KDNdVaKMpFZJwxavCxyeFnG7XUGY9hWJhHE2EtC6aU1IHFXWZin7aoTanUjL45z6U6EdLdbVUby2t7Id_B3sm_3rIHwB7x5u0</recordid><startdate>20240901</startdate><enddate>20240901</enddate><creator>Gu, Sun Mi</creator><creator>Hong, Eunchong</creator><creator>Seo, Sowoon</creator><creator>Kim, Sanghyeon</creator><creator>Yoon, Seong Shoon</creator><creator>Cha, Hye Jin</creator><creator>Yun, Jaesuk</creator><general>The Korean Society of Veterinary Science</general><general>대한수의학회</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><scope>ACYCR</scope><orcidid>https://orcid.org/0000-0002-3093-8919</orcidid><orcidid>https://orcid.org/0000-0002-7907-0487</orcidid><orcidid>https://orcid.org/0009-0007-4882-6492</orcidid><orcidid>https://orcid.org/0009-0006-8239-9570</orcidid><orcidid>https://orcid.org/0009-0003-8823-3035</orcidid><orcidid>https://orcid.org/0000-0002-8182-1024</orcidid><orcidid>https://orcid.org/0009-0002-9523-0759</orcidid></search><sort><creationdate>20240901</creationdate><title>Different development patterns of reward behaviors induced by ketamine and JWH-018 in striatal GAD67 knockdown mice</title><author>Gu, Sun Mi ; Hong, Eunchong ; Seo, Sowoon ; Kim, Sanghyeon ; Yoon, Seong Shoon ; Cha, Hye Jin ; Yun, Jaesuk</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c301t-9271f07ba0451224e31220e4df2c4f9169861e3e38091f23ed37da979d5538263</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Anxiety</topic><topic>Corpus Striatum - drug effects</topic><topic>Corpus Striatum - metabolism</topic><topic>Depression - chemically induced</topic><topic>Gene Knockdown Techniques</topic><topic>Glutamate Decarboxylase - genetics</topic><topic>Glutamate Decarboxylase - metabolism</topic><topic>Indoles - pharmacology</topic><topic>Ketamine - pharmacology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Naphthalenes - pharmacology</topic><topic>Research Report</topic><topic>Reward</topic><topic>수의학</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gu, Sun Mi</creatorcontrib><creatorcontrib>Hong, Eunchong</creatorcontrib><creatorcontrib>Seo, Sowoon</creatorcontrib><creatorcontrib>Kim, Sanghyeon</creatorcontrib><creatorcontrib>Yoon, Seong Shoon</creatorcontrib><creatorcontrib>Cha, Hye Jin</creatorcontrib><creatorcontrib>Yun, Jaesuk</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Korean Citation Index</collection><jtitle>Journal of veterinary science (Suwŏn-si, Korea)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gu, Sun Mi</au><au>Hong, Eunchong</au><au>Seo, Sowoon</au><au>Kim, Sanghyeon</au><au>Yoon, Seong Shoon</au><au>Cha, Hye Jin</au><au>Yun, Jaesuk</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Different development patterns of reward behaviors induced by ketamine and JWH-018 in striatal GAD67 knockdown mice</atitle><jtitle>Journal of veterinary science (Suwŏn-si, Korea)</jtitle><addtitle>J Vet Sci</addtitle><date>2024-09-01</date><risdate>2024</risdate><volume>25</volume><issue>5</issue><spage>e63</spage><epage>0</epage><pages>e63-0</pages><issn>1229-845X</issn><issn>1976-555X</issn><eissn>1976-555X</eissn><abstract>Glutamic acid decarboxylase 67 (GAD67) is a gamma-aminobutyric acid (GABA) synthesis enzyme associated with the function of other neurotransmitter receptors, such as the N-methyl-D-aspartate (NMDA) receptor and cannabinoid receptor 1. However, the role of GAD67 in the development of different abused drug-induced reward behaviors remains unknown. In order to elucidate the mechanisms of substance use disorder, it is crucial to study changes in biomarkers within the brain's reward circuit induced by drug use.
The study was designed to examine the effects of the downregulation of GAD67 expression in the dorsal striatum on reward behavior development.
We evaluated the effects of GAD67 knockdown on depression-like behavior and anxiety using the forced swim test and elevated plus maze test in a mouse model. We further determined the effects of GAD67 knockdown on ketamine- and JWH-018-induced conditioned place preference (CPP).
Knockdown of GAD67 in the dorsal striatum of mice increased depression-like behavior, but it decreased anxiety. Moreover, the CPP score on the NMDA receptor antagonist ketamine was increased by GAD67 knockdown, whereas the administration of JWH-018, a cannabinoid receptor agonist, did not affect the CPP score in the GAD67 knockdown mice group compared with the control group.
These results suggest that striatal GAD67 reduces GABAergic neuronal activity and may cause ketamine-induced NMDA receptor inhibition. Consequently, GAD67 downregulation induces vulnerability to the drug reward behavior of ketamine.</abstract><cop>Korea (South)</cop><pub>The Korean Society of Veterinary Science</pub><pmid>39231788</pmid><doi>10.4142/jvs.23325</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-3093-8919</orcidid><orcidid>https://orcid.org/0000-0002-7907-0487</orcidid><orcidid>https://orcid.org/0009-0007-4882-6492</orcidid><orcidid>https://orcid.org/0009-0006-8239-9570</orcidid><orcidid>https://orcid.org/0009-0003-8823-3035</orcidid><orcidid>https://orcid.org/0000-0002-8182-1024</orcidid><orcidid>https://orcid.org/0009-0002-9523-0759</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Animals Anxiety Corpus Striatum - drug effects Corpus Striatum - metabolism Depression - chemically induced Gene Knockdown Techniques Glutamate Decarboxylase - genetics Glutamate Decarboxylase - metabolism Indoles - pharmacology Ketamine - pharmacology Male Mice Mice, Inbred C57BL Naphthalenes - pharmacology Research Report Reward 수의학 |
title | Different development patterns of reward behaviors induced by ketamine and JWH-018 in striatal GAD67 knockdown mice |
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