Paradoxical effects of very low dose MK-801
Systemic injection of the noncompetitive NMDA ( N-methyl- d-aspartate) receptor antagonist MK-801 (dizocilpine maleate) is known to cause increased locomotion and various stereotypic behaviors in rodents. However, the MK-801 dose ranges commonly examined usually begin at tenth of mg/kg and going hig...
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| Veröffentlicht in: | European journal of pharmacology 2006-05, Vol.537 (1), p.77-84 |
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| container_title | European journal of pharmacology |
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| creator | Tang, Yuanjia Zou, Hong Strong, Judith A. Cui, Yiwen Xie, Qinglian Zhao, Guoping Jin, Meilei Yu, Lei |
| description | Systemic injection of the noncompetitive NMDA (
N-methyl-
d-aspartate) receptor antagonist MK-801 (dizocilpine maleate) is known to cause increased locomotion and various stereotypic behaviors in rodents. However, the MK-801 dose ranges commonly examined usually begin at tenth of mg/kg and going higher, with the implicit assumption of lower doses being ineffective. We report here that very low dose MK-801, well below the commonly studied doses, exert distinct effects on rodent behaviors. In C57BL/6 mice, very low dose MK-801 (0.02 mg/kg) has strikingly different effects than higher doses commonly reported in the literature. Locomotion, rearing, grooming, and other behaviors are strongly inhibited, replaced by periods of immobility. This is in contrast to the mobility-enhancing effect of MK-801 at commonly reported dose ranges. The effects of very low dose MK-801 are qualitatively similar to those observed with moderate doses (0.1–0.2 mg/kg) of the typical antipsychotic haloperidol. These results highlight the complexity of the dose–response relation for MK-801-induced behaviors. |
| doi_str_mv | 10.1016/j.ejphar.2006.03.016 |
| format | Article |
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N-methyl-
d-aspartate) receptor antagonist MK-801 (dizocilpine maleate) is known to cause increased locomotion and various stereotypic behaviors in rodents. However, the MK-801 dose ranges commonly examined usually begin at tenth of mg/kg and going higher, with the implicit assumption of lower doses being ineffective. We report here that very low dose MK-801, well below the commonly studied doses, exert distinct effects on rodent behaviors. In C57BL/6 mice, very low dose MK-801 (0.02 mg/kg) has strikingly different effects than higher doses commonly reported in the literature. Locomotion, rearing, grooming, and other behaviors are strongly inhibited, replaced by periods of immobility. This is in contrast to the mobility-enhancing effect of MK-801 at commonly reported dose ranges. The effects of very low dose MK-801 are qualitatively similar to those observed with moderate doses (0.1–0.2 mg/kg) of the typical antipsychotic haloperidol. These results highlight the complexity of the dose–response relation for MK-801-induced behaviors.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2006.03.016</identifier><identifier>PMID: 16626696</identifier><identifier>CODEN: EJPHAZ</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Animals ; Behavior, Animal - drug effects ; Biological and medical sciences ; Catalepsy ; Catalepsy - chemically induced ; Dizocilpine maleate ; Dizocilpine Maleate - pharmacology ; Excitatory Amino Acid Antagonists - pharmacology ; Haloperidol ; Immobility ; Locomotion ; Male ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Motor Activity - drug effects ; NMDA receptor antagonist ; Pharmacology. Drug treatments ; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</subject><ispartof>European journal of pharmacology, 2006-05, Vol.537 (1), p.77-84</ispartof><rights>2006</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c446t-c55273787985db72daf44abdb88c4b6602f9418106e1c50b05bc7728e37841d03</citedby><cites>FETCH-LOGICAL-c446t-c55273787985db72daf44abdb88c4b6602f9418106e1c50b05bc7728e37841d03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejphar.2006.03.016$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17742421$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16626696$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tang, Yuanjia</creatorcontrib><creatorcontrib>Zou, Hong</creatorcontrib><creatorcontrib>Strong, Judith A.</creatorcontrib><creatorcontrib>Cui, Yiwen</creatorcontrib><creatorcontrib>Xie, Qinglian</creatorcontrib><creatorcontrib>Zhao, Guoping</creatorcontrib><creatorcontrib>Jin, Meilei</creatorcontrib><creatorcontrib>Yu, Lei</creatorcontrib><title>Paradoxical effects of very low dose MK-801</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>Systemic injection of the noncompetitive NMDA (
N-methyl-
d-aspartate) receptor antagonist MK-801 (dizocilpine maleate) is known to cause increased locomotion and various stereotypic behaviors in rodents. However, the MK-801 dose ranges commonly examined usually begin at tenth of mg/kg and going higher, with the implicit assumption of lower doses being ineffective. We report here that very low dose MK-801, well below the commonly studied doses, exert distinct effects on rodent behaviors. In C57BL/6 mice, very low dose MK-801 (0.02 mg/kg) has strikingly different effects than higher doses commonly reported in the literature. Locomotion, rearing, grooming, and other behaviors are strongly inhibited, replaced by periods of immobility. This is in contrast to the mobility-enhancing effect of MK-801 at commonly reported dose ranges. The effects of very low dose MK-801 are qualitatively similar to those observed with moderate doses (0.1–0.2 mg/kg) of the typical antipsychotic haloperidol. These results highlight the complexity of the dose–response relation for MK-801-induced behaviors.</description><subject>Animals</subject><subject>Behavior, Animal - drug effects</subject><subject>Biological and medical sciences</subject><subject>Catalepsy</subject><subject>Catalepsy - chemically induced</subject><subject>Dizocilpine maleate</subject><subject>Dizocilpine Maleate - pharmacology</subject><subject>Excitatory Amino Acid Antagonists - pharmacology</subject><subject>Haloperidol</subject><subject>Immobility</subject><subject>Locomotion</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Motor Activity - drug effects</subject><subject>NMDA receptor antagonist</subject><subject>Pharmacology. Drug treatments</subject><subject>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kF1LwzAUhoMobk7_gUhv9EZaT9I0aW8EGX7hRC_0OqTJKbZ060y26f69GS3szqsDL8_7cngIOaeQUKDipkmwWX5plzAAkUCahPCAjGkuixgkZYdkDEB5zIqiGJET7xsAyAqWHZMRFYIJUYgxuX7XTtvutza6jbCq0Kx81FXRBt02arufyHYeo9eXOAd6So4q3Xo8G-6EfD7cf0yf4tnb4_P0bhYbzsUqNlnGZCrDH3lmS8msrjjXpS3z3PBSCGBVwWlOQSA1GZSQlUZKlmPocGohnZCrfnfpuu81-pWa195g2-oFdmuvqKSSFzINIO9B4zrvHVZq6eq5dltFQe0kqUb1ktROkoJUhTDULob9dTlHuy8NVgJwOQDaBy-V0wtT-z0nJWec0cDd9hwGG5sanfKmxoVBW7sgUtmu_v-TPwNog6w</recordid><startdate>20060510</startdate><enddate>20060510</enddate><creator>Tang, Yuanjia</creator><creator>Zou, Hong</creator><creator>Strong, Judith A.</creator><creator>Cui, Yiwen</creator><creator>Xie, Qinglian</creator><creator>Zhao, Guoping</creator><creator>Jin, Meilei</creator><creator>Yu, Lei</creator><general>Elsevier B.V</general><general>Elsevier</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>7U7</scope><scope>C1K</scope></search><sort><creationdate>20060510</creationdate><title>Paradoxical effects of very low dose MK-801</title><author>Tang, Yuanjia ; Zou, Hong ; Strong, Judith A. ; Cui, Yiwen ; Xie, Qinglian ; Zhao, Guoping ; Jin, Meilei ; Yu, Lei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c446t-c55273787985db72daf44abdb88c4b6602f9418106e1c50b05bc7728e37841d03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Behavior, Animal - drug effects</topic><topic>Biological and medical sciences</topic><topic>Catalepsy</topic><topic>Catalepsy - chemically induced</topic><topic>Dizocilpine maleate</topic><topic>Dizocilpine Maleate - pharmacology</topic><topic>Excitatory Amino Acid Antagonists - pharmacology</topic><topic>Haloperidol</topic><topic>Immobility</topic><topic>Locomotion</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Motor Activity - drug effects</topic><topic>NMDA receptor antagonist</topic><topic>Pharmacology. Drug treatments</topic><topic>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tang, Yuanjia</creatorcontrib><creatorcontrib>Zou, Hong</creatorcontrib><creatorcontrib>Strong, Judith A.</creatorcontrib><creatorcontrib>Cui, Yiwen</creatorcontrib><creatorcontrib>Xie, Qinglian</creatorcontrib><creatorcontrib>Zhao, Guoping</creatorcontrib><creatorcontrib>Jin, Meilei</creatorcontrib><creatorcontrib>Yu, Lei</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>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tang, Yuanjia</au><au>Zou, Hong</au><au>Strong, Judith A.</au><au>Cui, Yiwen</au><au>Xie, Qinglian</au><au>Zhao, Guoping</au><au>Jin, Meilei</au><au>Yu, Lei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Paradoxical effects of very low dose MK-801</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2006-05-10</date><risdate>2006</risdate><volume>537</volume><issue>1</issue><spage>77</spage><epage>84</epage><pages>77-84</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract>Systemic injection of the noncompetitive NMDA (
N-methyl-
d-aspartate) receptor antagonist MK-801 (dizocilpine maleate) is known to cause increased locomotion and various stereotypic behaviors in rodents. However, the MK-801 dose ranges commonly examined usually begin at tenth of mg/kg and going higher, with the implicit assumption of lower doses being ineffective. We report here that very low dose MK-801, well below the commonly studied doses, exert distinct effects on rodent behaviors. In C57BL/6 mice, very low dose MK-801 (0.02 mg/kg) has strikingly different effects than higher doses commonly reported in the literature. Locomotion, rearing, grooming, and other behaviors are strongly inhibited, replaced by periods of immobility. This is in contrast to the mobility-enhancing effect of MK-801 at commonly reported dose ranges. The effects of very low dose MK-801 are qualitatively similar to those observed with moderate doses (0.1–0.2 mg/kg) of the typical antipsychotic haloperidol. These results highlight the complexity of the dose–response relation for MK-801-induced behaviors.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>16626696</pmid><doi>10.1016/j.ejphar.2006.03.016</doi><tpages>8</tpages></addata></record> |
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| subjects | Animals Behavior, Animal - drug effects Biological and medical sciences Catalepsy Catalepsy - chemically induced Dizocilpine maleate Dizocilpine Maleate - pharmacology Excitatory Amino Acid Antagonists - pharmacology Haloperidol Immobility Locomotion Male Medical sciences Mice Mice, Inbred C57BL Motor Activity - drug effects NMDA receptor antagonist Pharmacology. Drug treatments Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors |
| title | Paradoxical effects of very low dose MK-801 |
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