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Sub-optimal performance in the 5-choice serial reaction time task in rats was sensitive to methylphenidate, atomoxetine and d-amphetamine, but unaffected by the COMT inhibitor tolcapone
▶ PFC dopamine and norepinephrine are implicated in impulsivity deficits. ▶ Prolonged ITI induced high levels of impulsivity in rats in 5-CSRTT. ▶ Tolcapone selectively enhances PFC dopamine, not norepinephrine. ▶ The COMT inhibitor tolcapone had no effects on the increased impulsivity. ▶ Data sugge...
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| Published in: | Neuroscience research 2011, Vol.69 (1), p.41-50 |
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| creator | Paterson, Neil E. Ricciardi, Jennifer Wetzler, Caitlin Hanania, Taleen |
| description | ▶ PFC dopamine and norepinephrine are implicated in impulsivity deficits. ▶ Prolonged ITI induced high levels of impulsivity in rats in 5-CSRTT. ▶ Tolcapone selectively enhances PFC dopamine, not norepinephrine. ▶ The COMT inhibitor tolcapone had no effects on the increased impulsivity. ▶ Data suggest PFC dopamine is not involved in impulsivity deficits in the 5-CSRTT.
Prefrontal cortical dopamine (DA) and norepinephrine (NE) are implicated in multiple aspects of cognitive function assessed via the 5-choice serial reaction time task (5-CSRTT) in rodents. The present studies assessed the effects of the NE reuptake inhibitor atomoxetine (0.5–2.0
mg/kg), the mixed DA/NE reuptake inhibitor methylphenidate (0.1–2.0
mg/kg), the catecholamine releaser
d-amphetamine (0.1–1.0
mg/kg) and the catecholamine-o-methyl-transferase (COMT) inhibitor tolcapone (3.0–30.0
mg/kg) in rats that exhibited sub-optimal performance (reduced accuracy: |
| doi_str_mv | 10.1016/j.neures.2010.10.001 |
| format | article |
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Prefrontal cortical dopamine (DA) and norepinephrine (NE) are implicated in multiple aspects of cognitive function assessed via the 5-choice serial reaction time task (5-CSRTT) in rodents. The present studies assessed the effects of the NE reuptake inhibitor atomoxetine (0.5–2.0
mg/kg), the mixed DA/NE reuptake inhibitor methylphenidate (0.1–2.0
mg/kg), the catecholamine releaser
d-amphetamine (0.1–1.0
mg/kg) and the catecholamine-o-methyl-transferase (COMT) inhibitor tolcapone (3.0–30.0
mg/kg) in rats that exhibited sub-optimal performance (reduced accuracy: <70% correct) in the 5-CSRTT. Increased ITI durations were associated with increased premature responding. Decreased ITI durations resulted in increased percent omissions, increased perseverative responses and increased response latencies, but had no effects on magazine latencies or percent correct. Atomoxetine decreased premature responding at prolonged ITI durations and methylphenidate decreased percent omissions at low doses (0.1 and 0.5
mg/kg). By contrast,
d-amphetamine increased premature and perseverative responding in a dose-dependent manner (0.3–1.0
mg/kg). Finally, tolcapone had no effects on sub-optimal performance in the variable ITI 5-CSRTT. These results suggest minimal potential of tolcapone as a therapeutic agent for ADHD and implicate cortical NE, not DA, in impulsive action.</description><identifier>ISSN: 0168-0102</identifier><identifier>EISSN: 1872-8111</identifier><identifier>DOI: 10.1016/j.neures.2010.10.001</identifier><identifier>PMID: 20934466</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>5-CSRTT ; Adrenergic Uptake Inhibitors - pharmacology ; Animals ; Atomoxetine ; Atomoxetine Hydrochloride ; Attention ; Attention - drug effects ; Attention - physiology ; Benzophenones - pharmacology ; Catechol O-Methyltransferase Inhibitors ; Central Nervous System Stimulants - pharmacology ; Choice Behavior - drug effects ; Choice Behavior - physiology ; d-Amphetamine ; Dextroamphetamine - pharmacology ; Dopamine - pharmacology ; Dopamine Uptake Inhibitors - pharmacology ; Dose-Response Relationship, Drug ; Impulsive Behavior - drug therapy ; Impulsivity ; Male ; Methylphenidate ; Methylphenidate - pharmacology ; Nitrophenols - pharmacology ; Norepinephrine - pharmacology ; Prefrontal Cortex - drug effects ; Propylamines - pharmacology ; Rat ; Rats ; Rats, Long-Evans ; Reaction Time - drug effects ; Reaction Time - physiology ; Tolcapone ; Variable inter-trial interval</subject><ispartof>Neuroscience research, 2011, Vol.69 (1), p.41-50</ispartof><rights>2010</rights><rights>Copyright © 2010. Published by Elsevier Ireland Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c512t-a5079b8e18900c9113717e3b622e3af775a53a502cbfcd4db8106fca4c5089853</citedby><cites>FETCH-LOGICAL-c512t-a5079b8e18900c9113717e3b622e3af775a53a502cbfcd4db8106fca4c5089853</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0168010210028130$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3549,4024,27923,27924,27925,45780</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20934466$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Paterson, Neil E.</creatorcontrib><creatorcontrib>Ricciardi, Jennifer</creatorcontrib><creatorcontrib>Wetzler, Caitlin</creatorcontrib><creatorcontrib>Hanania, Taleen</creatorcontrib><title>Sub-optimal performance in the 5-choice serial reaction time task in rats was sensitive to methylphenidate, atomoxetine and d-amphetamine, but unaffected by the COMT inhibitor tolcapone</title><title>Neuroscience research</title><addtitle>Neurosci Res</addtitle><description>▶ PFC dopamine and norepinephrine are implicated in impulsivity deficits. ▶ Prolonged ITI induced high levels of impulsivity in rats in 5-CSRTT. ▶ Tolcapone selectively enhances PFC dopamine, not norepinephrine. ▶ The COMT inhibitor tolcapone had no effects on the increased impulsivity. ▶ Data suggest PFC dopamine is not involved in impulsivity deficits in the 5-CSRTT.
Prefrontal cortical dopamine (DA) and norepinephrine (NE) are implicated in multiple aspects of cognitive function assessed via the 5-choice serial reaction time task (5-CSRTT) in rodents. The present studies assessed the effects of the NE reuptake inhibitor atomoxetine (0.5–2.0
mg/kg), the mixed DA/NE reuptake inhibitor methylphenidate (0.1–2.0
mg/kg), the catecholamine releaser
d-amphetamine (0.1–1.0
mg/kg) and the catecholamine-o-methyl-transferase (COMT) inhibitor tolcapone (3.0–30.0
mg/kg) in rats that exhibited sub-optimal performance (reduced accuracy: <70% correct) in the 5-CSRTT. Increased ITI durations were associated with increased premature responding. Decreased ITI durations resulted in increased percent omissions, increased perseverative responses and increased response latencies, but had no effects on magazine latencies or percent correct. Atomoxetine decreased premature responding at prolonged ITI durations and methylphenidate decreased percent omissions at low doses (0.1 and 0.5
mg/kg). By contrast,
d-amphetamine increased premature and perseverative responding in a dose-dependent manner (0.3–1.0
mg/kg). Finally, tolcapone had no effects on sub-optimal performance in the variable ITI 5-CSRTT. These results suggest minimal potential of tolcapone as a therapeutic agent for ADHD and implicate cortical NE, not DA, in impulsive action.</description><subject>5-CSRTT</subject><subject>Adrenergic Uptake Inhibitors - pharmacology</subject><subject>Animals</subject><subject>Atomoxetine</subject><subject>Atomoxetine Hydrochloride</subject><subject>Attention</subject><subject>Attention - drug effects</subject><subject>Attention - physiology</subject><subject>Benzophenones - pharmacology</subject><subject>Catechol O-Methyltransferase Inhibitors</subject><subject>Central Nervous System Stimulants - pharmacology</subject><subject>Choice Behavior - drug effects</subject><subject>Choice Behavior - physiology</subject><subject>d-Amphetamine</subject><subject>Dextroamphetamine - pharmacology</subject><subject>Dopamine - pharmacology</subject><subject>Dopamine Uptake Inhibitors - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Impulsive Behavior - drug therapy</subject><subject>Impulsivity</subject><subject>Male</subject><subject>Methylphenidate</subject><subject>Methylphenidate - pharmacology</subject><subject>Nitrophenols - pharmacology</subject><subject>Norepinephrine - pharmacology</subject><subject>Prefrontal Cortex - drug effects</subject><subject>Propylamines - pharmacology</subject><subject>Rat</subject><subject>Rats</subject><subject>Rats, Long-Evans</subject><subject>Reaction Time - drug effects</subject><subject>Reaction Time - physiology</subject><subject>Tolcapone</subject><subject>Variable inter-trial interval</subject><issn>0168-0102</issn><issn>1872-8111</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNqFkcuO1DAQRS0EYpqBP0DIOzaTxo7zcDZIqMVLGjQLhrVVsSuKm8QOtjNDfxp_h7t7YAkry3VP1S3VJeQlZ1vOePNmv3W4Bozbkp1KW8b4I7Lhsi0LyTl_TDYZk0VWywvyLMY9Y0x0lXhKLkrWiapqmg359XXtC78kO8NEFwyDDzM4jdQ6mkakdaFHb_M_YrAZCQg6WZ9FOyNNEL8fyQAp0nuImXLRJnuXJU9nTONhWkZ01kDCKwrJz_4nJuuQgjPUFDBnOcGcK1e0XxNdHQwD6oSG9ofTBrubL7fZY7S9TT7kuZOGxTt8Tp4MMEV88fBekm8f3t_uPhXXNx8_795dF7rmZSqgZm3XS-SyY0x3nIuWtyj6pixRwNC2NdQiQ6XuB20q00vOmkFDpWsmO1mLS_L6PHcJ_seKManZRo3TBA79GpVsmGi7upP_J3kjZFUxnsnqTOrgYww4qCXkBMJBcaaO6aq9Oqerjukeq-zU9urBYO1nNH-b_sSZgbdnAPNB7iwGFbXFHKexIR9VGW__7fAbNSq6-g</recordid><startdate>2011</startdate><enddate>2011</enddate><creator>Paterson, Neil E.</creator><creator>Ricciardi, Jennifer</creator><creator>Wetzler, Caitlin</creator><creator>Hanania, Taleen</creator><general>Elsevier Ireland Ltd</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>7X8</scope><scope>7TK</scope></search><sort><creationdate>2011</creationdate><title>Sub-optimal performance in the 5-choice serial reaction time task in rats was sensitive to methylphenidate, atomoxetine and d-amphetamine, but unaffected by the COMT inhibitor tolcapone</title><author>Paterson, Neil E. ; Ricciardi, Jennifer ; Wetzler, Caitlin ; Hanania, Taleen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c512t-a5079b8e18900c9113717e3b622e3af775a53a502cbfcd4db8106fca4c5089853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>5-CSRTT</topic><topic>Adrenergic Uptake Inhibitors - pharmacology</topic><topic>Animals</topic><topic>Atomoxetine</topic><topic>Atomoxetine Hydrochloride</topic><topic>Attention</topic><topic>Attention - drug effects</topic><topic>Attention - physiology</topic><topic>Benzophenones - pharmacology</topic><topic>Catechol O-Methyltransferase Inhibitors</topic><topic>Central Nervous System Stimulants - pharmacology</topic><topic>Choice Behavior - drug effects</topic><topic>Choice Behavior - physiology</topic><topic>d-Amphetamine</topic><topic>Dextroamphetamine - pharmacology</topic><topic>Dopamine - pharmacology</topic><topic>Dopamine Uptake Inhibitors - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Impulsive Behavior - drug therapy</topic><topic>Impulsivity</topic><topic>Male</topic><topic>Methylphenidate</topic><topic>Methylphenidate - pharmacology</topic><topic>Nitrophenols - pharmacology</topic><topic>Norepinephrine - pharmacology</topic><topic>Prefrontal Cortex - drug effects</topic><topic>Propylamines - pharmacology</topic><topic>Rat</topic><topic>Rats</topic><topic>Rats, Long-Evans</topic><topic>Reaction Time - drug effects</topic><topic>Reaction Time - physiology</topic><topic>Tolcapone</topic><topic>Variable inter-trial interval</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Paterson, Neil E.</creatorcontrib><creatorcontrib>Ricciardi, Jennifer</creatorcontrib><creatorcontrib>Wetzler, Caitlin</creatorcontrib><creatorcontrib>Hanania, Taleen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><jtitle>Neuroscience research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Paterson, Neil E.</au><au>Ricciardi, Jennifer</au><au>Wetzler, Caitlin</au><au>Hanania, Taleen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sub-optimal performance in the 5-choice serial reaction time task in rats was sensitive to methylphenidate, atomoxetine and d-amphetamine, but unaffected by the COMT inhibitor tolcapone</atitle><jtitle>Neuroscience research</jtitle><addtitle>Neurosci Res</addtitle><date>2011</date><risdate>2011</risdate><volume>69</volume><issue>1</issue><spage>41</spage><epage>50</epage><pages>41-50</pages><issn>0168-0102</issn><eissn>1872-8111</eissn><abstract>▶ PFC dopamine and norepinephrine are implicated in impulsivity deficits. ▶ Prolonged ITI induced high levels of impulsivity in rats in 5-CSRTT. ▶ Tolcapone selectively enhances PFC dopamine, not norepinephrine. ▶ The COMT inhibitor tolcapone had no effects on the increased impulsivity. ▶ Data suggest PFC dopamine is not involved in impulsivity deficits in the 5-CSRTT.
Prefrontal cortical dopamine (DA) and norepinephrine (NE) are implicated in multiple aspects of cognitive function assessed via the 5-choice serial reaction time task (5-CSRTT) in rodents. The present studies assessed the effects of the NE reuptake inhibitor atomoxetine (0.5–2.0
mg/kg), the mixed DA/NE reuptake inhibitor methylphenidate (0.1–2.0
mg/kg), the catecholamine releaser
d-amphetamine (0.1–1.0
mg/kg) and the catecholamine-o-methyl-transferase (COMT) inhibitor tolcapone (3.0–30.0
mg/kg) in rats that exhibited sub-optimal performance (reduced accuracy: <70% correct) in the 5-CSRTT. Increased ITI durations were associated with increased premature responding. Decreased ITI durations resulted in increased percent omissions, increased perseverative responses and increased response latencies, but had no effects on magazine latencies or percent correct. Atomoxetine decreased premature responding at prolonged ITI durations and methylphenidate decreased percent omissions at low doses (0.1 and 0.5
mg/kg). By contrast,
d-amphetamine increased premature and perseverative responding in a dose-dependent manner (0.3–1.0
mg/kg). Finally, tolcapone had no effects on sub-optimal performance in the variable ITI 5-CSRTT. These results suggest minimal potential of tolcapone as a therapeutic agent for ADHD and implicate cortical NE, not DA, in impulsive action.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>20934466</pmid><doi>10.1016/j.neures.2010.10.001</doi><tpages>10</tpages></addata></record> |
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| subjects | 5-CSRTT Adrenergic Uptake Inhibitors - pharmacology Animals Atomoxetine Atomoxetine Hydrochloride Attention Attention - drug effects Attention - physiology Benzophenones - pharmacology Catechol O-Methyltransferase Inhibitors Central Nervous System Stimulants - pharmacology Choice Behavior - drug effects Choice Behavior - physiology d-Amphetamine Dextroamphetamine - pharmacology Dopamine - pharmacology Dopamine Uptake Inhibitors - pharmacology Dose-Response Relationship, Drug Impulsive Behavior - drug therapy Impulsivity Male Methylphenidate Methylphenidate - pharmacology Nitrophenols - pharmacology Norepinephrine - pharmacology Prefrontal Cortex - drug effects Propylamines - pharmacology Rat Rats Rats, Long-Evans Reaction Time - drug effects Reaction Time - physiology Tolcapone Variable inter-trial interval |
| title | Sub-optimal performance in the 5-choice serial reaction time task in rats was sensitive to methylphenidate, atomoxetine and d-amphetamine, but unaffected by the COMT inhibitor tolcapone |
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