Differential effects of two NMDA receptor antagonists on cognitive–behavioral performance in young nonhuman primates II
The present experiment examined the effects of chronic exposure to remacemide (an NMDA antagonist that also blocks fast sodium channels) or MK-801 (which blocks NMDA receptors more selectively) on the acquisition of color and position discrimination and short-term memory behavior in juvenile rhesus...
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| Veröffentlicht in: | Neurotoxicology and teratology 2001-07, Vol.23 (4), p.333-347 |
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| creator | Popke, E.J Allen, R.R Pearson, E.C Hammond, T.G Paule, M.G |
| description | The present experiment examined the effects of chronic exposure to remacemide (an NMDA antagonist that also blocks fast sodium channels) or MK-801 (which blocks NMDA receptors more selectively) on the acquisition of color and position discrimination and short-term memory behavior in juvenile rhesus monkeys. Throughout the 2-year dosing period, a conditioned position responding (CPR) task was used to assess color and position discrimination and a delayed matching-to-sample (DMTS) task was used to assess memory. Chronic exposure to high doses of either drug delayed the acquisition of accurate color and position discrimination without altering response rates. In the case of MK-801, these effects abated within 6 months of the start of treatment. In the case of remacemide, the effects persisted for 17 months of dosing. Neither compound significantly altered performance of the short-term memory task at any time point or at any dose tested. The fact that the effects of remacemide on behavioral performance were more persistent than those seen for MK-801 suggests that tolerance may develop to the behavioral effects of MK-801, which does not develop to the effects of remacemide. Alternatively, these results may suggest that the concurrent antagonism of NMDA receptors and fast sodium channels may have more profound consequences for behavior than does the antagonism of NMDA receptors alone. |
| doi_str_mv | 10.1016/S0892-0362(01)00138-6 |
| format | Article |
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Throughout the 2-year dosing period, a conditioned position responding (CPR) task was used to assess color and position discrimination and a delayed matching-to-sample (DMTS) task was used to assess memory. Chronic exposure to high doses of either drug delayed the acquisition of accurate color and position discrimination without altering response rates. In the case of MK-801, these effects abated within 6 months of the start of treatment. In the case of remacemide, the effects persisted for 17 months of dosing. Neither compound significantly altered performance of the short-term memory task at any time point or at any dose tested. The fact that the effects of remacemide on behavioral performance were more persistent than those seen for MK-801 suggests that tolerance may develop to the behavioral effects of MK-801, which does not develop to the effects of remacemide. Alternatively, these results may suggest that the concurrent antagonism of NMDA receptors and fast sodium channels may have more profound consequences for behavior than does the antagonism of NMDA receptors alone.</description><identifier>ISSN: 0892-0362</identifier><identifier>EISSN: 1872-9738</identifier><identifier>DOI: 10.1016/S0892-0362(01)00138-6</identifier><identifier>PMID: 11485836</identifier><identifier>CODEN: NETEEC</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Acetamides - pharmacology ; Animals ; Biological and medical sciences ; Cognition - drug effects ; Color and position discrimination ; Color Perception - drug effects ; Color Perception - physiology ; Conditioning, Operant - drug effects ; Discrimination (Psychology) - drug effects ; dizocilpine maleate ; Dizocilpine Maleate - pharmacology ; Dose-Response Relationship, Drug ; Drug toxicity and drugs side effects treatment ; Fast sodium channels ; Female ; Macaca mulatta ; Medical sciences ; Memory, Short-Term - drug effects ; Memory, Short-Term - physiology ; MK-801 ; N-methyl- d-aspartate (NMDA) ; Neuroprotective Agents - pharmacology ; Operant behavior ; Pharmacology. Drug treatments ; Pregnancy ; Prenatal Exposure Delayed Effects ; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors ; Remacemide ; Restraint, Physical ; Reward ; Rhesus monkeys ; Short-term memory ; Substance Withdrawal Syndrome ; Toxicity: nervous system and muscle</subject><ispartof>Neurotoxicology and teratology, 2001-07, Vol.23 (4), p.333-347</ispartof><rights>2001 Elsevier Science Inc.</rights><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c468t-8eac05b3da92da264cb3f8e71a8764391a4ae7352f19dc483af1f7f0fa4fbab53</citedby><cites>FETCH-LOGICAL-c468t-8eac05b3da92da264cb3f8e71a8764391a4ae7352f19dc483af1f7f0fa4fbab53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0892-0362(01)00138-6$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,782,786,3552,27931,27932,46002</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1068671$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11485836$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Popke, E.J</creatorcontrib><creatorcontrib>Allen, R.R</creatorcontrib><creatorcontrib>Pearson, E.C</creatorcontrib><creatorcontrib>Hammond, T.G</creatorcontrib><creatorcontrib>Paule, M.G</creatorcontrib><title>Differential effects of two NMDA receptor antagonists on cognitive–behavioral performance in young nonhuman primates II</title><title>Neurotoxicology and teratology</title><addtitle>Neurotoxicol Teratol</addtitle><description>The present experiment examined the effects of chronic exposure to remacemide (an NMDA antagonist that also blocks fast sodium channels) or MK-801 (which blocks NMDA receptors more selectively) on the acquisition of color and position discrimination and short-term memory behavior in juvenile rhesus monkeys. Throughout the 2-year dosing period, a conditioned position responding (CPR) task was used to assess color and position discrimination and a delayed matching-to-sample (DMTS) task was used to assess memory. Chronic exposure to high doses of either drug delayed the acquisition of accurate color and position discrimination without altering response rates. In the case of MK-801, these effects abated within 6 months of the start of treatment. In the case of remacemide, the effects persisted for 17 months of dosing. Neither compound significantly altered performance of the short-term memory task at any time point or at any dose tested. The fact that the effects of remacemide on behavioral performance were more persistent than those seen for MK-801 suggests that tolerance may develop to the behavioral effects of MK-801, which does not develop to the effects of remacemide. Alternatively, these results may suggest that the concurrent antagonism of NMDA receptors and fast sodium channels may have more profound consequences for behavior than does the antagonism of NMDA receptors alone.</description><subject>Acetamides - pharmacology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cognition - drug effects</subject><subject>Color and position discrimination</subject><subject>Color Perception - drug effects</subject><subject>Color Perception - physiology</subject><subject>Conditioning, Operant - drug effects</subject><subject>Discrimination (Psychology) - drug effects</subject><subject>dizocilpine maleate</subject><subject>Dizocilpine Maleate - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug toxicity and drugs side effects treatment</subject><subject>Fast sodium channels</subject><subject>Female</subject><subject>Macaca mulatta</subject><subject>Medical sciences</subject><subject>Memory, Short-Term - drug effects</subject><subject>Memory, Short-Term - physiology</subject><subject>MK-801</subject><subject>N-methyl- d-aspartate (NMDA)</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Operant behavior</subject><subject>Pharmacology. Drug treatments</subject><subject>Pregnancy</subject><subject>Prenatal Exposure Delayed Effects</subject><subject>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</subject><subject>Remacemide</subject><subject>Restraint, Physical</subject><subject>Reward</subject><subject>Rhesus monkeys</subject><subject>Short-term memory</subject><subject>Substance Withdrawal Syndrome</subject><subject>Toxicity: nervous system and muscle</subject><issn>0892-0362</issn><issn>1872-9738</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUuO1DAQhi0EYpqBI4C8QAgWATtOHGeFRjM8WhpgAaytilPuMUrbPbbTqHfcgRtyEtwPATtWLllf_VX6ipDHnL3kjMtXn5nq64oJWT9n_AVjXKhK3iELrrq66juh7pLFH-SMPEjpG2Osk5zdJ2ecN6pVQi7I7spZixF9djBRLLXJiQZL8_dAP364uqARDW5yiBR8hlXwLu0BT01YeZfdFn_9-DngDWxdiCVig9GGuAZvkDpPd2H2K-qDv5nLH91Et4aMiS6XD8k9C1PCR6f3nHx9--bL5fvq-tO75eXFdWUaqXKlEAxrBzFCX49Qy8YMwirsOKhONqLn0AB2oq0t70fTKAGW284yC40dYGjFOXl2zN3EcDtjynrtksFpAo9hTpqrmgkhZAHbI2hiSCmi1Ydt405zpvfO9cG53gvVjOuDc73ve3IaMA9rHP92nSQX4OkJgGRgsrHIcemfdKlkxwv2-ohhsbF1GHUyDovH0ZUbZD0G959NfgNSlqFg</recordid><startdate>20010701</startdate><enddate>20010701</enddate><creator>Popke, E.J</creator><creator>Allen, R.R</creator><creator>Pearson, E.C</creator><creator>Hammond, T.G</creator><creator>Paule, M.G</creator><general>Elsevier Inc</general><general>Elsevier Science</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>7TK</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20010701</creationdate><title>Differential effects of two NMDA receptor antagonists on cognitive–behavioral performance in young nonhuman primates II</title><author>Popke, E.J ; Allen, R.R ; Pearson, E.C ; Hammond, T.G ; Paule, M.G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c468t-8eac05b3da92da264cb3f8e71a8764391a4ae7352f19dc483af1f7f0fa4fbab53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Acetamides - pharmacology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cognition - drug effects</topic><topic>Color and position discrimination</topic><topic>Color Perception - drug effects</topic><topic>Color Perception - physiology</topic><topic>Conditioning, Operant - drug effects</topic><topic>Discrimination (Psychology) - drug effects</topic><topic>dizocilpine maleate</topic><topic>Dizocilpine Maleate - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug toxicity and drugs side effects treatment</topic><topic>Fast sodium channels</topic><topic>Female</topic><topic>Macaca mulatta</topic><topic>Medical sciences</topic><topic>Memory, Short-Term - drug effects</topic><topic>Memory, Short-Term - physiology</topic><topic>MK-801</topic><topic>N-methyl- d-aspartate (NMDA)</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Operant behavior</topic><topic>Pharmacology. Drug treatments</topic><topic>Pregnancy</topic><topic>Prenatal Exposure Delayed Effects</topic><topic>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</topic><topic>Remacemide</topic><topic>Restraint, Physical</topic><topic>Reward</topic><topic>Rhesus monkeys</topic><topic>Short-term memory</topic><topic>Substance Withdrawal Syndrome</topic><topic>Toxicity: nervous system and muscle</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Popke, E.J</creatorcontrib><creatorcontrib>Allen, R.R</creatorcontrib><creatorcontrib>Pearson, E.C</creatorcontrib><creatorcontrib>Hammond, T.G</creatorcontrib><creatorcontrib>Paule, M.G</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>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Neurotoxicology and teratology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Popke, E.J</au><au>Allen, R.R</au><au>Pearson, E.C</au><au>Hammond, T.G</au><au>Paule, M.G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differential effects of two NMDA receptor antagonists on cognitive–behavioral performance in young nonhuman primates II</atitle><jtitle>Neurotoxicology and teratology</jtitle><addtitle>Neurotoxicol Teratol</addtitle><date>2001-07-01</date><risdate>2001</risdate><volume>23</volume><issue>4</issue><spage>333</spage><epage>347</epage><pages>333-347</pages><issn>0892-0362</issn><eissn>1872-9738</eissn><coden>NETEEC</coden><abstract>The present experiment examined the effects of chronic exposure to remacemide (an NMDA antagonist that also blocks fast sodium channels) or MK-801 (which blocks NMDA receptors more selectively) on the acquisition of color and position discrimination and short-term memory behavior in juvenile rhesus monkeys. Throughout the 2-year dosing period, a conditioned position responding (CPR) task was used to assess color and position discrimination and a delayed matching-to-sample (DMTS) task was used to assess memory. Chronic exposure to high doses of either drug delayed the acquisition of accurate color and position discrimination without altering response rates. In the case of MK-801, these effects abated within 6 months of the start of treatment. In the case of remacemide, the effects persisted for 17 months of dosing. Neither compound significantly altered performance of the short-term memory task at any time point or at any dose tested. The fact that the effects of remacemide on behavioral performance were more persistent than those seen for MK-801 suggests that tolerance may develop to the behavioral effects of MK-801, which does not develop to the effects of remacemide. Alternatively, these results may suggest that the concurrent antagonism of NMDA receptors and fast sodium channels may have more profound consequences for behavior than does the antagonism of NMDA receptors alone.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>11485836</pmid><doi>10.1016/S0892-0362(01)00138-6</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acetamides - pharmacology Animals Biological and medical sciences Cognition - drug effects Color and position discrimination Color Perception - drug effects Color Perception - physiology Conditioning, Operant - drug effects Discrimination (Psychology) - drug effects dizocilpine maleate Dizocilpine Maleate - pharmacology Dose-Response Relationship, Drug Drug toxicity and drugs side effects treatment Fast sodium channels Female Macaca mulatta Medical sciences Memory, Short-Term - drug effects Memory, Short-Term - physiology MK-801 N-methyl- d-aspartate (NMDA) Neuroprotective Agents - pharmacology Operant behavior Pharmacology. Drug treatments Pregnancy Prenatal Exposure Delayed Effects Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors Remacemide Restraint, Physical Reward Rhesus monkeys Short-term memory Substance Withdrawal Syndrome Toxicity: nervous system and muscle |
| title | Differential effects of two NMDA receptor antagonists on cognitive–behavioral performance in young nonhuman primates II |
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