Behavioural and biochemical responses to morphine associated with its motivational properties are altered in adenosine A(2A) receptor knockout mice
The purinergic system through the A(2A) adenosine receptor regulates addiction induced by different drugs of abuse. The aim of the present study was to investigate the specific role of A(2A) adenosine receptors (A(2A)Rs) in the behavioural and neurochemical responses to morphine associated with its...
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| Veröffentlicht in: | British journal of pharmacology 2008-11, Vol.155 (5), p.757-766 |
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| container_title | British journal of pharmacology |
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| creator | Castañé, A Wells, L Soria, G Hourani, S Ledent, C Kitchen, I Opacka-Juffry, J Maldonado, R Valverde, O |
| description | The purinergic system through the A(2A) adenosine receptor regulates addiction induced by different drugs of abuse. The aim of the present study was to investigate the specific role of A(2A) adenosine receptors (A(2A)Rs) in the behavioural and neurochemical responses to morphine associated with its motivational properties.
Mice lacking A(2A)Rs (A(2A) knockout (KO) mice) and wild-type littermates were used to evaluate behavioural responses induced by morphine. Antinociception was assessed using the tail-immersion and the hot-plate tests. Place-conditioning paradigms were used to evaluate the rewarding effects of morphine and the dysphoric responses of morphine withdrawal. Microdialysis studies were carried out to evaluate changes in the extracellular levels of dopamine in the nucleus accumbens of A(2A) KO mice after morphine administration.
The acute administration of morphine induced a similar enhancement of locomotor activity and antinociceptive responses in both genotypes. However, the rewarding effects induced by morphine were completely blocked in A(2A) KO mice. Also, naloxone did not induce place aversion in animals lacking the A(2A)Rs.
Our findings demonstrate that the rewarding and aversive effects associated with morphine abstinence were abolished in A(2A) KO mice, supporting a differential role of the A(2A) adenosine receptor in the somatic and motivational effects of morphine addiction. This study provides evidence for the role of A(2A)Rs as general modulators of the motivational properties of drugs of abuse. Pharmacological manipulation of these receptors may represent a new target in the management of drug addiction. |
| doi_str_mv | 10.1038/bjp.2008.299 |
| format | Article |
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Mice lacking A(2A)Rs (A(2A) knockout (KO) mice) and wild-type littermates were used to evaluate behavioural responses induced by morphine. Antinociception was assessed using the tail-immersion and the hot-plate tests. Place-conditioning paradigms were used to evaluate the rewarding effects of morphine and the dysphoric responses of morphine withdrawal. Microdialysis studies were carried out to evaluate changes in the extracellular levels of dopamine in the nucleus accumbens of A(2A) KO mice after morphine administration.
The acute administration of morphine induced a similar enhancement of locomotor activity and antinociceptive responses in both genotypes. However, the rewarding effects induced by morphine were completely blocked in A(2A) KO mice. Also, naloxone did not induce place aversion in animals lacking the A(2A)Rs.
Our findings demonstrate that the rewarding and aversive effects associated with morphine abstinence were abolished in A(2A) KO mice, supporting a differential role of the A(2A) adenosine receptor in the somatic and motivational effects of morphine addiction. This study provides evidence for the role of A(2A)Rs as general modulators of the motivational properties of drugs of abuse. Pharmacological manipulation of these receptors may represent a new target in the management of drug addiction.</description><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1038/bjp.2008.299</identifier><identifier>PMID: 18660831</identifier><language>eng</language><publisher>England</publisher><subject>Animals ; Behavior, Animal - drug effects ; Behavior, Animal - physiology ; Dopamine - metabolism ; Male ; Mice ; Mice, Knockout ; Microdialysis ; Morphine - pharmacology ; Motivation ; Motor Activity - drug effects ; Nucleus Accumbens - metabolism ; Nucleus Accumbens - physiology ; Pain Threshold - drug effects ; Receptor, Adenosine A2A - genetics ; Receptor, Adenosine A2A - physiology</subject><ispartof>British journal of pharmacology, 2008-11, Vol.155 (5), p.757-766</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18660831$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Castañé, A</creatorcontrib><creatorcontrib>Wells, L</creatorcontrib><creatorcontrib>Soria, G</creatorcontrib><creatorcontrib>Hourani, S</creatorcontrib><creatorcontrib>Ledent, C</creatorcontrib><creatorcontrib>Kitchen, I</creatorcontrib><creatorcontrib>Opacka-Juffry, J</creatorcontrib><creatorcontrib>Maldonado, R</creatorcontrib><creatorcontrib>Valverde, O</creatorcontrib><title>Behavioural and biochemical responses to morphine associated with its motivational properties are altered in adenosine A(2A) receptor knockout mice</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>The purinergic system through the A(2A) adenosine receptor regulates addiction induced by different drugs of abuse. The aim of the present study was to investigate the specific role of A(2A) adenosine receptors (A(2A)Rs) in the behavioural and neurochemical responses to morphine associated with its motivational properties.
Mice lacking A(2A)Rs (A(2A) knockout (KO) mice) and wild-type littermates were used to evaluate behavioural responses induced by morphine. Antinociception was assessed using the tail-immersion and the hot-plate tests. Place-conditioning paradigms were used to evaluate the rewarding effects of morphine and the dysphoric responses of morphine withdrawal. Microdialysis studies were carried out to evaluate changes in the extracellular levels of dopamine in the nucleus accumbens of A(2A) KO mice after morphine administration.
The acute administration of morphine induced a similar enhancement of locomotor activity and antinociceptive responses in both genotypes. However, the rewarding effects induced by morphine were completely blocked in A(2A) KO mice. Also, naloxone did not induce place aversion in animals lacking the A(2A)Rs.
Our findings demonstrate that the rewarding and aversive effects associated with morphine abstinence were abolished in A(2A) KO mice, supporting a differential role of the A(2A) adenosine receptor in the somatic and motivational effects of morphine addiction. This study provides evidence for the role of A(2A)Rs as general modulators of the motivational properties of drugs of abuse. Pharmacological manipulation of these receptors may represent a new target in the management of drug addiction.</description><subject>Animals</subject><subject>Behavior, Animal - drug effects</subject><subject>Behavior, Animal - physiology</subject><subject>Dopamine - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Microdialysis</subject><subject>Morphine - pharmacology</subject><subject>Motivation</subject><subject>Motor Activity - drug effects</subject><subject>Nucleus Accumbens - metabolism</subject><subject>Nucleus Accumbens - physiology</subject><subject>Pain Threshold - drug effects</subject><subject>Receptor, Adenosine A2A - genetics</subject><subject>Receptor, Adenosine A2A - physiology</subject><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1UDtPwzAQtpAQLYWNGXlCMLTYsZvYY6l4SZVYYI5s56q4TWJjOyB-B38YI8p0urvvcfchdEHJghImbvXOLwpCxKKQ8ghNKa_K-ZIJOkGnMe4IyYNqeYImVJQlEYxO0fcdtOrDujGoDquhwdo600JvTe4DRO-GCBEnh3sXfGsHwCpGZ6xK0OBPm1psU8zLZD9Usm7INB-ch5Bs5qmQ8V2CkMF2wKqBwcVfkdV1sbrJBgZ8cgHvB2f2bkw4G8MZOt6qLsL5oc7Q28P96_ppvnl5fF6vNnNPmUzz_DEhlZCglSBcSs63mldaSLrVihNRMqhoUTEJDa-WlBhKTUFLQxhvtCgbNkNXf7r54PcRYqp7Gw10nRrAjbEuZUV5ji8DLw_AUffQ1D7YXoWv-j9G9gMs_HSC</recordid><startdate>200811</startdate><enddate>200811</enddate><creator>Castañé, A</creator><creator>Wells, L</creator><creator>Soria, G</creator><creator>Hourani, S</creator><creator>Ledent, C</creator><creator>Kitchen, I</creator><creator>Opacka-Juffry, J</creator><creator>Maldonado, R</creator><creator>Valverde, O</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>200811</creationdate><title>Behavioural and biochemical responses to morphine associated with its motivational properties are altered in adenosine A(2A) receptor knockout mice</title><author>Castañé, A ; Wells, L ; Soria, G ; Hourani, S ; Ledent, C ; Kitchen, I ; Opacka-Juffry, J ; Maldonado, R ; Valverde, O</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p139t-10300789eba8049944fb47b891fba40863e712739ed47510c11c216c034db86d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Behavior, Animal - drug effects</topic><topic>Behavior, Animal - physiology</topic><topic>Dopamine - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Microdialysis</topic><topic>Morphine - pharmacology</topic><topic>Motivation</topic><topic>Motor Activity - drug effects</topic><topic>Nucleus Accumbens - metabolism</topic><topic>Nucleus Accumbens - physiology</topic><topic>Pain Threshold - drug effects</topic><topic>Receptor, Adenosine A2A - genetics</topic><topic>Receptor, Adenosine A2A - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Castañé, A</creatorcontrib><creatorcontrib>Wells, L</creatorcontrib><creatorcontrib>Soria, G</creatorcontrib><creatorcontrib>Hourani, S</creatorcontrib><creatorcontrib>Ledent, C</creatorcontrib><creatorcontrib>Kitchen, I</creatorcontrib><creatorcontrib>Opacka-Juffry, J</creatorcontrib><creatorcontrib>Maldonado, R</creatorcontrib><creatorcontrib>Valverde, O</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Castañé, A</au><au>Wells, L</au><au>Soria, G</au><au>Hourani, S</au><au>Ledent, C</au><au>Kitchen, I</au><au>Opacka-Juffry, J</au><au>Maldonado, R</au><au>Valverde, O</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Behavioural and biochemical responses to morphine associated with its motivational properties are altered in adenosine A(2A) receptor knockout mice</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>2008-11</date><risdate>2008</risdate><volume>155</volume><issue>5</issue><spage>757</spage><epage>766</epage><pages>757-766</pages><eissn>1476-5381</eissn><abstract>The purinergic system through the A(2A) adenosine receptor regulates addiction induced by different drugs of abuse. The aim of the present study was to investigate the specific role of A(2A) adenosine receptors (A(2A)Rs) in the behavioural and neurochemical responses to morphine associated with its motivational properties.
Mice lacking A(2A)Rs (A(2A) knockout (KO) mice) and wild-type littermates were used to evaluate behavioural responses induced by morphine. Antinociception was assessed using the tail-immersion and the hot-plate tests. Place-conditioning paradigms were used to evaluate the rewarding effects of morphine and the dysphoric responses of morphine withdrawal. Microdialysis studies were carried out to evaluate changes in the extracellular levels of dopamine in the nucleus accumbens of A(2A) KO mice after morphine administration.
The acute administration of morphine induced a similar enhancement of locomotor activity and antinociceptive responses in both genotypes. However, the rewarding effects induced by morphine were completely blocked in A(2A) KO mice. Also, naloxone did not induce place aversion in animals lacking the A(2A)Rs.
Our findings demonstrate that the rewarding and aversive effects associated with morphine abstinence were abolished in A(2A) KO mice, supporting a differential role of the A(2A) adenosine receptor in the somatic and motivational effects of morphine addiction. This study provides evidence for the role of A(2A)Rs as general modulators of the motivational properties of drugs of abuse. Pharmacological manipulation of these receptors may represent a new target in the management of drug addiction.</abstract><cop>England</cop><pmid>18660831</pmid><doi>10.1038/bjp.2008.299</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Behavior, Animal - drug effects Behavior, Animal - physiology Dopamine - metabolism Male Mice Mice, Knockout Microdialysis Morphine - pharmacology Motivation Motor Activity - drug effects Nucleus Accumbens - metabolism Nucleus Accumbens - physiology Pain Threshold - drug effects Receptor, Adenosine A2A - genetics Receptor, Adenosine A2A - physiology |
| title | Behavioural and biochemical responses to morphine associated with its motivational properties are altered in adenosine A(2A) receptor knockout mice |
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