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Intravenous self-administration of the cannabinoid CB1 receptor agonist WIN 55,212-2 in rats
Delta9-tetrahydrocannabinol (Delta9-THC), the main psychoactive ingredient of marijuana, as well as synthetic cannabinoid (CB1) receptor agonists, has led to negative or equivocal results when tested with the intravenous self-administration procedure, the best validated behavioural model for evaluat...
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| Published in: | Psychopharmacologia 2001-08, Vol.156 (4), p.410-416 |
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| Main Authors: | , , , |
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| Language: | English |
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| container_end_page | 416 |
| container_issue | 4 |
| container_start_page | 410 |
| container_title | Psychopharmacologia |
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| creator | FATTORE, Liana COSSU, Gregorio MARTELLOTTA, Cristina M FRATTA, Walter |
| description | Delta9-tetrahydrocannabinol (Delta9-THC), the main psychoactive ingredient of marijuana, as well as synthetic cannabinoid (CB1) receptor agonists, has led to negative or equivocal results when tested with the intravenous self-administration procedure, the best validated behavioural model for evaluating abuse liability of drugs in experimental animals. We recently reported, however, that the synthetic CB1 receptor agonist WIN 55,212-2 is intravenously self-administered by drug-naive mice and that its self-administration is blocked by the cannabinoid CB1 receptor antagonist SR 141716A.
To assess a reliable model of cannabinoid intravenous self-administration in rats. Long Evans male rats were allowed the opportunity to self-administer WIN 55,212-2 at doses ranging from 6.25 to 50 microg/kg per injection, under a fixed-ratio 1 (FR1) schedule of reinforcement and nose-pokes as the operant responses. The effect of either a change in the unit drug dose available or a pretreatment with the specific CB1 receptor antagonist SR 141716A were then investigated (maintenance phase). Finally, the extinction of the self-administration behaviour was evaluated.
Response rate depended on the drug dose available, with maximum rates occurring at 12.5 microg/kg per injection. Response rate increased following pretreatment with the specific CB1 receptor antagonist, SR 141716A. Moreover, operant behaviour rapidly extinguished following both the substitution of saline or vehicle for cannabinoid and the disconnection of the drug delivery pumps.
Rats will intravenously self-administer the synthetic CB1 receptor agonist WIN 55,212-2 under specific experimental conditions, thus allowing further investigation of the neurobiological mechanisms underlying cannabinoid-taking behaviour. |
| doi_str_mv | 10.1007/s002130100734 |
| format | article |
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To assess a reliable model of cannabinoid intravenous self-administration in rats. Long Evans male rats were allowed the opportunity to self-administer WIN 55,212-2 at doses ranging from 6.25 to 50 microg/kg per injection, under a fixed-ratio 1 (FR1) schedule of reinforcement and nose-pokes as the operant responses. The effect of either a change in the unit drug dose available or a pretreatment with the specific CB1 receptor antagonist SR 141716A were then investigated (maintenance phase). Finally, the extinction of the self-administration behaviour was evaluated.
Response rate depended on the drug dose available, with maximum rates occurring at 12.5 microg/kg per injection. Response rate increased following pretreatment with the specific CB1 receptor antagonist, SR 141716A. Moreover, operant behaviour rapidly extinguished following both the substitution of saline or vehicle for cannabinoid and the disconnection of the drug delivery pumps.
Rats will intravenously self-administer the synthetic CB1 receptor agonist WIN 55,212-2 under specific experimental conditions, thus allowing further investigation of the neurobiological mechanisms underlying cannabinoid-taking behaviour.</description><identifier>ISSN: 0033-3158</identifier><identifier>EISSN: 1432-2072</identifier><identifier>DOI: 10.1007/s002130100734</identifier><identifier>PMID: 11498718</identifier><identifier>CODEN: PSYPAG</identifier><language>eng</language><publisher>Berlin: Springer</publisher><subject>Analgesics - administration & dosage ; Analgesics - pharmacology ; Animals ; Benzoxazines ; Biological and medical sciences ; Cannabinoids - metabolism ; Dose-Response Relationship, Drug ; Drug addictions ; Injections, Intravenous ; Male ; Medical sciences ; Morpholines - administration & dosage ; Morpholines - pharmacology ; Naphthalenes - administration & dosage ; Naphthalenes - pharmacology ; Piperidines - pharmacology ; Pyrazoles - pharmacology ; Rats ; Rats, Long-Evans ; Receptors, Cannabinoid ; Receptors, Drug - agonists ; Receptors, Drug - antagonists & inhibitors ; Reinforcement Schedule ; Rimonabant ; Self Administration - psychology ; Substance Abuse, Intravenous - psychology ; Toxicology ; WIN 55,212-2</subject><ispartof>Psychopharmacologia, 2001-08, Vol.156 (4), p.410-416</ispartof><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-b3d79fab92d9ec2d1a0c48c91a909a29e06bf355d1bad627254994f8faf4a2363</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1083765$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11498718$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>FATTORE, Liana</creatorcontrib><creatorcontrib>COSSU, Gregorio</creatorcontrib><creatorcontrib>MARTELLOTTA, Cristina M</creatorcontrib><creatorcontrib>FRATTA, Walter</creatorcontrib><title>Intravenous self-administration of the cannabinoid CB1 receptor agonist WIN 55,212-2 in rats</title><title>Psychopharmacologia</title><addtitle>Psychopharmacology (Berl)</addtitle><description>Delta9-tetrahydrocannabinol (Delta9-THC), the main psychoactive ingredient of marijuana, as well as synthetic cannabinoid (CB1) receptor agonists, has led to negative or equivocal results when tested with the intravenous self-administration procedure, the best validated behavioural model for evaluating abuse liability of drugs in experimental animals. We recently reported, however, that the synthetic CB1 receptor agonist WIN 55,212-2 is intravenously self-administered by drug-naive mice and that its self-administration is blocked by the cannabinoid CB1 receptor antagonist SR 141716A.
To assess a reliable model of cannabinoid intravenous self-administration in rats. Long Evans male rats were allowed the opportunity to self-administer WIN 55,212-2 at doses ranging from 6.25 to 50 microg/kg per injection, under a fixed-ratio 1 (FR1) schedule of reinforcement and nose-pokes as the operant responses. The effect of either a change in the unit drug dose available or a pretreatment with the specific CB1 receptor antagonist SR 141716A were then investigated (maintenance phase). Finally, the extinction of the self-administration behaviour was evaluated.
Response rate depended on the drug dose available, with maximum rates occurring at 12.5 microg/kg per injection. Response rate increased following pretreatment with the specific CB1 receptor antagonist, SR 141716A. Moreover, operant behaviour rapidly extinguished following both the substitution of saline or vehicle for cannabinoid and the disconnection of the drug delivery pumps.
Rats will intravenously self-administer the synthetic CB1 receptor agonist WIN 55,212-2 under specific experimental conditions, thus allowing further investigation of the neurobiological mechanisms underlying cannabinoid-taking behaviour.</description><subject>Analgesics - administration & dosage</subject><subject>Analgesics - pharmacology</subject><subject>Animals</subject><subject>Benzoxazines</subject><subject>Biological and medical sciences</subject><subject>Cannabinoids - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug addictions</subject><subject>Injections, Intravenous</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Morpholines - administration & dosage</subject><subject>Morpholines - pharmacology</subject><subject>Naphthalenes - administration & dosage</subject><subject>Naphthalenes - pharmacology</subject><subject>Piperidines - pharmacology</subject><subject>Pyrazoles - pharmacology</subject><subject>Rats</subject><subject>Rats, Long-Evans</subject><subject>Receptors, Cannabinoid</subject><subject>Receptors, Drug - agonists</subject><subject>Receptors, Drug - antagonists & inhibitors</subject><subject>Reinforcement Schedule</subject><subject>Rimonabant</subject><subject>Self Administration - psychology</subject><subject>Substance Abuse, Intravenous - psychology</subject><subject>Toxicology</subject><subject>WIN 55,212-2</subject><issn>0033-3158</issn><issn>1432-2072</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><recordid>eNpVkM1LxDAQxYMo7rp69Co5iCer-WqbHHXxY2HRi-JFKNM00UibrklX8L83yxbUucww_N4b5iF0TMkFJaS8jIQwyslm5mIHTangLGOkZLtoSgjnGae5nKCDGD9IKiHFPppQKpQsqZyi14UfAnwZ368jjqa1GTSd8y6m7eB6j3uLh3eDNXgPtfO9a_D8muJgtFkNfcDw1m9o_LJ4wHl-zmi6jp3HSR4P0Z6FNpqjsc_Q8-3N0_w-Wz7eLeZXy0wLmg9ZzZtSWagVa5TRrKFAtJBaUVBEAVOGFLXled7QGpqClSwXSgkrLVgBjBd8hs62vqvQf65NHKrORW3aFrxJf1W0lEkgRQKzLahDH2MwtloF10H4riipNhFW_-JM_MlovK470_zSY34JOB0BiBpaG8BrF_-4Sl4WOf8Bsj166w</recordid><startdate>20010801</startdate><enddate>20010801</enddate><creator>FATTORE, Liana</creator><creator>COSSU, Gregorio</creator><creator>MARTELLOTTA, Cristina M</creator><creator>FRATTA, Walter</creator><general>Springer</general><scope>IQODW</scope><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>7TK</scope></search><sort><creationdate>20010801</creationdate><title>Intravenous self-administration of the cannabinoid CB1 receptor agonist WIN 55,212-2 in rats</title><author>FATTORE, Liana ; COSSU, Gregorio ; MARTELLOTTA, Cristina M ; FRATTA, Walter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-b3d79fab92d9ec2d1a0c48c91a909a29e06bf355d1bad627254994f8faf4a2363</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Analgesics - administration & dosage</topic><topic>Analgesics - pharmacology</topic><topic>Animals</topic><topic>Benzoxazines</topic><topic>Biological and medical sciences</topic><topic>Cannabinoids - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug addictions</topic><topic>Injections, Intravenous</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Morpholines - administration & dosage</topic><topic>Morpholines - pharmacology</topic><topic>Naphthalenes - administration & dosage</topic><topic>Naphthalenes - pharmacology</topic><topic>Piperidines - pharmacology</topic><topic>Pyrazoles - pharmacology</topic><topic>Rats</topic><topic>Rats, Long-Evans</topic><topic>Receptors, Cannabinoid</topic><topic>Receptors, Drug - agonists</topic><topic>Receptors, Drug - antagonists & inhibitors</topic><topic>Reinforcement Schedule</topic><topic>Rimonabant</topic><topic>Self Administration - psychology</topic><topic>Substance Abuse, Intravenous - psychology</topic><topic>Toxicology</topic><topic>WIN 55,212-2</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>FATTORE, Liana</creatorcontrib><creatorcontrib>COSSU, Gregorio</creatorcontrib><creatorcontrib>MARTELLOTTA, Cristina M</creatorcontrib><creatorcontrib>FRATTA, Walter</creatorcontrib><collection>Pascal-Francis</collection><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>Neurosciences Abstracts</collection><jtitle>Psychopharmacologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>FATTORE, Liana</au><au>COSSU, Gregorio</au><au>MARTELLOTTA, Cristina M</au><au>FRATTA, Walter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intravenous self-administration of the cannabinoid CB1 receptor agonist WIN 55,212-2 in rats</atitle><jtitle>Psychopharmacologia</jtitle><addtitle>Psychopharmacology (Berl)</addtitle><date>2001-08-01</date><risdate>2001</risdate><volume>156</volume><issue>4</issue><spage>410</spage><epage>416</epage><pages>410-416</pages><issn>0033-3158</issn><eissn>1432-2072</eissn><coden>PSYPAG</coden><notes>ObjectType-Article-2</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-1</notes><notes>content type line 23</notes><abstract>Delta9-tetrahydrocannabinol (Delta9-THC), the main psychoactive ingredient of marijuana, as well as synthetic cannabinoid (CB1) receptor agonists, has led to negative or equivocal results when tested with the intravenous self-administration procedure, the best validated behavioural model for evaluating abuse liability of drugs in experimental animals. We recently reported, however, that the synthetic CB1 receptor agonist WIN 55,212-2 is intravenously self-administered by drug-naive mice and that its self-administration is blocked by the cannabinoid CB1 receptor antagonist SR 141716A.
To assess a reliable model of cannabinoid intravenous self-administration in rats. Long Evans male rats were allowed the opportunity to self-administer WIN 55,212-2 at doses ranging from 6.25 to 50 microg/kg per injection, under a fixed-ratio 1 (FR1) schedule of reinforcement and nose-pokes as the operant responses. The effect of either a change in the unit drug dose available or a pretreatment with the specific CB1 receptor antagonist SR 141716A were then investigated (maintenance phase). Finally, the extinction of the self-administration behaviour was evaluated.
Response rate depended on the drug dose available, with maximum rates occurring at 12.5 microg/kg per injection. Response rate increased following pretreatment with the specific CB1 receptor antagonist, SR 141716A. Moreover, operant behaviour rapidly extinguished following both the substitution of saline or vehicle for cannabinoid and the disconnection of the drug delivery pumps.
Rats will intravenously self-administer the synthetic CB1 receptor agonist WIN 55,212-2 under specific experimental conditions, thus allowing further investigation of the neurobiological mechanisms underlying cannabinoid-taking behaviour.</abstract><cop>Berlin</cop><pub>Springer</pub><pmid>11498718</pmid><doi>10.1007/s002130100734</doi><tpages>7</tpages></addata></record> |
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| ispartof | Psychopharmacologia, 2001-08, Vol.156 (4), p.410-416 |
| issn | 0033-3158 1432-2072 |
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| source | SPORTDiscus; Springer Link |
| subjects | Analgesics - administration & dosage Analgesics - pharmacology Animals Benzoxazines Biological and medical sciences Cannabinoids - metabolism Dose-Response Relationship, Drug Drug addictions Injections, Intravenous Male Medical sciences Morpholines - administration & dosage Morpholines - pharmacology Naphthalenes - administration & dosage Naphthalenes - pharmacology Piperidines - pharmacology Pyrazoles - pharmacology Rats Rats, Long-Evans Receptors, Cannabinoid Receptors, Drug - agonists Receptors, Drug - antagonists & inhibitors Reinforcement Schedule Rimonabant Self Administration - psychology Substance Abuse, Intravenous - psychology Toxicology WIN 55,212-2 |
| title | Intravenous self-administration of the cannabinoid CB1 receptor agonist WIN 55,212-2 in rats |
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