Modafinil rescues repeated morphine‐induced synaptic and behavioural impairments via activation of D1R–ERK–CREB pathway in medial prefrontal cortex
Long‐term opioid abuse causes a variety of long‐lasting cognitive impairments such as attention, impulsivity and working memory. These cognitive impairments undermine behavioural treatment for drug abuse and lead to poor treatment retention and outcomes. Modafinil is a wake‐promoting drug that shows...
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| Veröffentlicht in: | Addiction biology 2022-01, Vol.27 (1), p.e13103-n/a |
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| container_title | Addiction biology |
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| creator | Yin, Fangyuan Zhang, Jinyu Lu, Ye Zhang, Yulei Liu, Jincen Deji, Cuola Qiao, Xiaomeng Gao, Keqiang Xu, Min Lai, Jianghua Wang, Yunpeng |
| description | Long‐term opioid abuse causes a variety of long‐lasting cognitive impairments such as attention, impulsivity and working memory. These cognitive impairments undermine behavioural treatment for drug abuse and lead to poor treatment retention and outcomes. Modafinil is a wake‐promoting drug that shows potential in improving attention and memory in humans and animals. However, modafinil's effect on opioid‐induced cognitive impairments remains unclear, and the underlying mechanism is poorly understood. This study showed that repeated morphine administration significantly impairs attention, increases impulsivity and reduces motivation to natural rewards in mice. Systemic modafinil treatment at low dose efficiently ameliorates morphine‐induced attention dysfunction and improves motivation and working memory in mice. High dose of modafinil has adverse effects on impulsive action and attention. Local infusion of D1R antagonist SCH‐23390 reverses the morphine‐induced synaptic abnormalities and activation of the D1R–ERK–CREB pathway in medial prefrontal cortex (mPFC). This study demonstrated a protective effect of modafinil in mPFC neurons and offered a therapeutic potential for cognitive deficits in opioid abuse.
Systemic modafinil treatment at low dose efficiently ameliorated morphine‐induced attention dysfunction and improved motivation and working memory in mice. High modafinil dose had adverse effects on impulsive action and attention. By inhibiting dopamine uptake transporters, modafinil increased the dopamine levels in the synaptic cleft and enhanced the D1R–ERK–CREB signalling activity. |
| doi_str_mv | 10.1111/adb.13103 |
| format | Article |
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Systemic modafinil treatment at low dose efficiently ameliorated morphine‐induced attention dysfunction and improved motivation and working memory in mice. High modafinil dose had adverse effects on impulsive action and attention. By inhibiting dopamine uptake transporters, modafinil increased the dopamine levels in the synaptic cleft and enhanced the D1R–ERK–CREB signalling activity.</description><identifier>ISSN: 1355-6215</identifier><identifier>EISSN: 1369-1600</identifier><identifier>DOI: 10.1111/adb.13103</identifier><identifier>PMID: 34647651</identifier><language>eng</language><publisher>United States: John Wiley & Sons, Inc</publisher><subject>5‐CSRTT ; Animals ; Attention - drug effects ; Cognition Disorders - chemically induced ; Cognition Disorders - physiopathology ; Cognitive ability ; Cyclic AMP response element-binding protein ; Dose-Response Relationship, Drug ; Drug abuse ; Drug dosages ; Extracellular signal-regulated kinase ; Impulsive behavior ; Impulsive Behavior - drug effects ; Impulsivity ; MAP Kinase Signaling System - drug effects ; Memory ; Mice ; Modafinil ; Modafinil - administration & dosage ; Modafinil - adverse effects ; Modafinil - pharmacology ; Morphine ; Morphine - pharmacology ; Motivation ; Motivation - drug effects ; Narcotics ; Opioids ; Prefrontal cortex ; Prefrontal Cortex - drug effects ; Short term memory ; Substance abuse treatment</subject><ispartof>Addiction biology, 2022-01, Vol.27 (1), p.e13103-n/a</ispartof><rights>2021 Society for the Study of Addiction</rights><rights>2021 Society for the Study of Addiction.</rights><rights>2022 Society for the Study of Addiction</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3533-aa40007b1deafcc4ab2e90bc95bd2c636d164640552d7e3fc1452d2b37b089be3</citedby><cites>FETCH-LOGICAL-c3533-aa40007b1deafcc4ab2e90bc95bd2c636d164640552d7e3fc1452d2b37b089be3</cites><orcidid>0000-0003-3094-0266 ; 0000-0003-4291-4487</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fadb.13103$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fadb.13103$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34647651$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yin, Fangyuan</creatorcontrib><creatorcontrib>Zhang, Jinyu</creatorcontrib><creatorcontrib>Lu, Ye</creatorcontrib><creatorcontrib>Zhang, Yulei</creatorcontrib><creatorcontrib>Liu, Jincen</creatorcontrib><creatorcontrib>Deji, Cuola</creatorcontrib><creatorcontrib>Qiao, Xiaomeng</creatorcontrib><creatorcontrib>Gao, Keqiang</creatorcontrib><creatorcontrib>Xu, Min</creatorcontrib><creatorcontrib>Lai, Jianghua</creatorcontrib><creatorcontrib>Wang, Yunpeng</creatorcontrib><title>Modafinil rescues repeated morphine‐induced synaptic and behavioural impairments via activation of D1R–ERK–CREB pathway in medial prefrontal cortex</title><title>Addiction biology</title><addtitle>Addict Biol</addtitle><description>Long‐term opioid abuse causes a variety of long‐lasting cognitive impairments such as attention, impulsivity and working memory. These cognitive impairments undermine behavioural treatment for drug abuse and lead to poor treatment retention and outcomes. Modafinil is a wake‐promoting drug that shows potential in improving attention and memory in humans and animals. However, modafinil's effect on opioid‐induced cognitive impairments remains unclear, and the underlying mechanism is poorly understood. This study showed that repeated morphine administration significantly impairs attention, increases impulsivity and reduces motivation to natural rewards in mice. Systemic modafinil treatment at low dose efficiently ameliorates morphine‐induced attention dysfunction and improves motivation and working memory in mice. High dose of modafinil has adverse effects on impulsive action and attention. Local infusion of D1R antagonist SCH‐23390 reverses the morphine‐induced synaptic abnormalities and activation of the D1R–ERK–CREB pathway in medial prefrontal cortex (mPFC). This study demonstrated a protective effect of modafinil in mPFC neurons and offered a therapeutic potential for cognitive deficits in opioid abuse.
Systemic modafinil treatment at low dose efficiently ameliorated morphine‐induced attention dysfunction and improved motivation and working memory in mice. High modafinil dose had adverse effects on impulsive action and attention. By inhibiting dopamine uptake transporters, modafinil increased the dopamine levels in the synaptic cleft and enhanced the D1R–ERK–CREB signalling activity.</description><subject>5‐CSRTT</subject><subject>Animals</subject><subject>Attention - drug effects</subject><subject>Cognition Disorders - chemically induced</subject><subject>Cognition Disorders - physiopathology</subject><subject>Cognitive ability</subject><subject>Cyclic AMP response element-binding protein</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug abuse</subject><subject>Drug dosages</subject><subject>Extracellular signal-regulated kinase</subject><subject>Impulsive behavior</subject><subject>Impulsive Behavior - drug effects</subject><subject>Impulsivity</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Memory</subject><subject>Mice</subject><subject>Modafinil</subject><subject>Modafinil - administration & dosage</subject><subject>Modafinil - adverse effects</subject><subject>Modafinil - pharmacology</subject><subject>Morphine</subject><subject>Morphine - pharmacology</subject><subject>Motivation</subject><subject>Motivation - drug effects</subject><subject>Narcotics</subject><subject>Opioids</subject><subject>Prefrontal cortex</subject><subject>Prefrontal Cortex - drug effects</subject><subject>Short term memory</subject><subject>Substance abuse treatment</subject><issn>1355-6215</issn><issn>1369-1600</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1u1DAUhS0EoqWw4AWQJVZdpLXj2CHLdjrQilZII1hH1z_RuJrYwfZMmV0fAamrvl6fhFumsKsXvkfWp2MfH0Lec3bEcR2D1UdccCZekH0uVFdxxdjLRy1lpWou98ibnK8Z43UrxWuyJxrVtEryfXJ_FS0MPvgVTS6btcs4JwfFWTrGNC19cA-3v32wa4NHeRtgKt5QCJZqt4SNj-sEK-rHCXwaXSiZbjxQMMVvoPgYaBzoGV883N7NF19xny3mp3SCsryBLfWBjs56NJiSG1IMBaWJqbhfb8mrAVbZvXuaB-TH5_n32Xl1-e3LxezksjJCClEBNIyxVnPrYDCmAV27jmnTSW1ro4SyXGFaJmVtWycGwxtUtRatZp867cQB-bjznVL8iflLf42RAl7Z14rLuu140yJ1uKNMijnjW_sp-RHStuesfyyhxxL6vyUg--HJca0x3X_y368jcLwDbvzKbZ936k_OTneWfwCbupXn</recordid><startdate>202201</startdate><enddate>202201</enddate><creator>Yin, Fangyuan</creator><creator>Zhang, Jinyu</creator><creator>Lu, Ye</creator><creator>Zhang, Yulei</creator><creator>Liu, Jincen</creator><creator>Deji, Cuola</creator><creator>Qiao, Xiaomeng</creator><creator>Gao, Keqiang</creator><creator>Xu, Min</creator><creator>Lai, Jianghua</creator><creator>Wang, Yunpeng</creator><general>John Wiley & Sons, Inc</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>7QG</scope><scope>7T5</scope><scope>7TM</scope><scope>H94</scope><orcidid>https://orcid.org/0000-0003-3094-0266</orcidid><orcidid>https://orcid.org/0000-0003-4291-4487</orcidid></search><sort><creationdate>202201</creationdate><title>Modafinil rescues repeated morphine‐induced synaptic and behavioural impairments via activation of D1R–ERK–CREB pathway in medial prefrontal cortex</title><author>Yin, Fangyuan ; Zhang, Jinyu ; Lu, Ye ; Zhang, Yulei ; Liu, Jincen ; Deji, Cuola ; Qiao, Xiaomeng ; Gao, Keqiang ; Xu, Min ; Lai, Jianghua ; Wang, Yunpeng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3533-aa40007b1deafcc4ab2e90bc95bd2c636d164640552d7e3fc1452d2b37b089be3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>5‐CSRTT</topic><topic>Animals</topic><topic>Attention - drug effects</topic><topic>Cognition Disorders - chemically induced</topic><topic>Cognition Disorders - physiopathology</topic><topic>Cognitive ability</topic><topic>Cyclic AMP response element-binding protein</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug abuse</topic><topic>Drug dosages</topic><topic>Extracellular signal-regulated kinase</topic><topic>Impulsive behavior</topic><topic>Impulsive Behavior - drug effects</topic><topic>Impulsivity</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Memory</topic><topic>Mice</topic><topic>Modafinil</topic><topic>Modafinil - administration & dosage</topic><topic>Modafinil - adverse effects</topic><topic>Modafinil - pharmacology</topic><topic>Morphine</topic><topic>Morphine - pharmacology</topic><topic>Motivation</topic><topic>Motivation - drug effects</topic><topic>Narcotics</topic><topic>Opioids</topic><topic>Prefrontal cortex</topic><topic>Prefrontal Cortex - drug effects</topic><topic>Short term memory</topic><topic>Substance abuse treatment</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yin, Fangyuan</creatorcontrib><creatorcontrib>Zhang, Jinyu</creatorcontrib><creatorcontrib>Lu, Ye</creatorcontrib><creatorcontrib>Zhang, Yulei</creatorcontrib><creatorcontrib>Liu, Jincen</creatorcontrib><creatorcontrib>Deji, Cuola</creatorcontrib><creatorcontrib>Qiao, Xiaomeng</creatorcontrib><creatorcontrib>Gao, Keqiang</creatorcontrib><creatorcontrib>Xu, Min</creatorcontrib><creatorcontrib>Lai, Jianghua</creatorcontrib><creatorcontrib>Wang, Yunpeng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Addiction biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yin, Fangyuan</au><au>Zhang, Jinyu</au><au>Lu, Ye</au><au>Zhang, Yulei</au><au>Liu, Jincen</au><au>Deji, Cuola</au><au>Qiao, Xiaomeng</au><au>Gao, Keqiang</au><au>Xu, Min</au><au>Lai, Jianghua</au><au>Wang, Yunpeng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Modafinil rescues repeated morphine‐induced synaptic and behavioural impairments via activation of D1R–ERK–CREB pathway in medial prefrontal cortex</atitle><jtitle>Addiction biology</jtitle><addtitle>Addict Biol</addtitle><date>2022-01</date><risdate>2022</risdate><volume>27</volume><issue>1</issue><spage>e13103</spage><epage>n/a</epage><pages>e13103-n/a</pages><issn>1355-6215</issn><eissn>1369-1600</eissn><abstract>Long‐term opioid abuse causes a variety of long‐lasting cognitive impairments such as attention, impulsivity and working memory. These cognitive impairments undermine behavioural treatment for drug abuse and lead to poor treatment retention and outcomes. Modafinil is a wake‐promoting drug that shows potential in improving attention and memory in humans and animals. However, modafinil's effect on opioid‐induced cognitive impairments remains unclear, and the underlying mechanism is poorly understood. This study showed that repeated morphine administration significantly impairs attention, increases impulsivity and reduces motivation to natural rewards in mice. Systemic modafinil treatment at low dose efficiently ameliorates morphine‐induced attention dysfunction and improves motivation and working memory in mice. High dose of modafinil has adverse effects on impulsive action and attention. Local infusion of D1R antagonist SCH‐23390 reverses the morphine‐induced synaptic abnormalities and activation of the D1R–ERK–CREB pathway in medial prefrontal cortex (mPFC). This study demonstrated a protective effect of modafinil in mPFC neurons and offered a therapeutic potential for cognitive deficits in opioid abuse.
Systemic modafinil treatment at low dose efficiently ameliorated morphine‐induced attention dysfunction and improved motivation and working memory in mice. High modafinil dose had adverse effects on impulsive action and attention. By inhibiting dopamine uptake transporters, modafinil increased the dopamine levels in the synaptic cleft and enhanced the D1R–ERK–CREB signalling activity.</abstract><cop>United States</cop><pub>John Wiley & Sons, Inc</pub><pmid>34647651</pmid><doi>10.1111/adb.13103</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-3094-0266</orcidid><orcidid>https://orcid.org/0000-0003-4291-4487</orcidid></addata></record> |
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| subjects | 5‐CSRTT Animals Attention - drug effects Cognition Disorders - chemically induced Cognition Disorders - physiopathology Cognitive ability Cyclic AMP response element-binding protein Dose-Response Relationship, Drug Drug abuse Drug dosages Extracellular signal-regulated kinase Impulsive behavior Impulsive Behavior - drug effects Impulsivity MAP Kinase Signaling System - drug effects Memory Mice Modafinil Modafinil - administration & dosage Modafinil - adverse effects Modafinil - pharmacology Morphine Morphine - pharmacology Motivation Motivation - drug effects Narcotics Opioids Prefrontal cortex Prefrontal Cortex - drug effects Short term memory Substance abuse treatment |
| title | Modafinil rescues repeated morphine‐induced synaptic and behavioural impairments via activation of D1R–ERK–CREB pathway in medial prefrontal cortex |
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