The 5-HT 1A/1B -receptor agonist eltoprazine increases both catecholamine release in the prefrontal cortex and dopamine release in the nucleus accumbens and decreases motivation for reward and "waiting" impulsivity, but increases "stopping" impulsivity
The 5-HT -receptor agonist eltoprazine has a behavioral drug signature that resembles that of a variety of psychostimulant drugs, despite the differences in receptor binding profile. These psychostimulants are effective in treating impulsivity disorders, most likely because they increase norepinephr...
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| Veröffentlicht in: | European journal of pharmacology 2017-01, Vol.794, p.257 |
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| creator | Korte, S Mechiel Prins, Jolanda Van den Bergh, Filip S Oosting, Ronald S Dupree, Rudy Korte-Bouws, Gerdien A H Westphal, Koen G C Olivier, Berend Denys, Damiaan A Garland, Alexis Güntürkün, Onur |
| description | The 5-HT
-receptor agonist eltoprazine has a behavioral drug signature that resembles that of a variety of psychostimulant drugs, despite the differences in receptor binding profile. These psychostimulants are effective in treating impulsivity disorders, most likely because they increase norepinephrine (NE) and dopamine (DA) levels in the prefrontal cortex. Both amphetamine and methylphenidate, however, also increase dopamine levels in the nucleus accumbens (NAc), which has a significant role in motivation, pleasure, and reward. How eltoprazine affects monoamine release in the medial prefrontal cortex (mPFC), the orbitofrontal cortex (OFC), and the NAc is unknown. It is also unknown whether eltoprazine affects different forms of impulsivity and brain reward mechanisms. Therefore, in the present study, we investigate the effects of eltoprazine in rats in the following sequence: 1) the activity of the monoaminergic systems using in vivo microdialysis, 2) motivation for reward measured using the intracranial self-stimulation (ICSS) procedure, and finally, 3) "waiting" impulsivity in the delay-aversion task, and the "stopping" impulsivity in the stop-signal task. The microdialysis studies clearly showed that eltoprazine increased DA and NE release in both the mPFC and OFC, but only increased DA concentration in the NAc. In contrast, eltoprazine decreased 5-HT release in the mPFC and NAc (undetectable in the OFC). Remarkably, eltoprazine decreased impulsive choice, but increased impulsive action. Furthermore, brain stimulation was less rewarding following eltoprazine treatment. These results further support the long-standing hypothesis that "waiting" and "stopping" impulsivity are regulated by distinct neural circuits, because 5-HT
-receptor activation decreases impulsive choice, but increases impulsive action. |
| format | Article |
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-receptor activation decreases impulsive choice, but increases impulsive action.</description><subject>Animals</subject><subject>Choice Behavior - drug effects</subject><subject>Dopamine - secretion</subject><subject>Impulsive Behavior - drug effects</subject><subject>Male</subject><subject>Motivation - drug effects</subject><subject>Nucleus Accumbens - drug effects</subject><subject>Nucleus Accumbens - secretion</subject><subject>Piperazines - pharmacology</subject><subject>Prefrontal Cortex - drug effects</subject><subject>Prefrontal Cortex - secretion</subject><subject>Rats</subject><subject>Receptor, Serotonin, 5-HT1A - metabolism</subject><subject>Receptor, Serotonin, 5-HT1B - metabolism</subject><subject>Reward</subject><subject>Serotonin 5-HT1 Receptor Agonists - pharmacology</subject><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0EtLw0AQB_AgiK2PryBDzgaTSJrmqKL0A-ReJptJs7Ivdmdb62f3YKoWRARPc_j_mNdJMi-WdZPldVHOkvMQXvI8r5qyOktmZb1cLJqmmSfv7UhQZasWivvb4gEyT4IcWw-4sUYGBlJsncc3aQikEZ4wUIDO8ggCmcRoFepD6EkdsgkBT02dp8Fbw6hAWM_0Cmh66K37U5soFMUAKETUHZnwpek4T1uWW2RpDQzTcp526PtPk-5QsjSbFKR2UQW5lby_gS7yj3XTMB3hfqvL5HRAFejqu14k189P7eMqc7HT1K-dlxr9fn18192_4APj4Hx5</recordid><startdate>20170105</startdate><enddate>20170105</enddate><creator>Korte, S Mechiel</creator><creator>Prins, Jolanda</creator><creator>Van den Bergh, Filip S</creator><creator>Oosting, Ronald S</creator><creator>Dupree, Rudy</creator><creator>Korte-Bouws, Gerdien A H</creator><creator>Westphal, Koen G C</creator><creator>Olivier, Berend</creator><creator>Denys, Damiaan A</creator><creator>Garland, Alexis</creator><creator>Güntürkün, Onur</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>20170105</creationdate><title>The 5-HT 1A/1B -receptor agonist eltoprazine increases both catecholamine release in the prefrontal cortex and dopamine release in the nucleus accumbens and decreases motivation for reward and "waiting" impulsivity, but increases "stopping" impulsivity</title><author>Korte, S Mechiel ; Prins, Jolanda ; Van den Bergh, Filip S ; Oosting, Ronald S ; Dupree, Rudy ; Korte-Bouws, Gerdien A H ; Westphal, Koen G C ; Olivier, Berend ; Denys, Damiaan A ; Garland, Alexis ; Güntürkün, Onur</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-pubmed_primary_278669993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Choice Behavior - drug effects</topic><topic>Dopamine - secretion</topic><topic>Impulsive Behavior - drug effects</topic><topic>Male</topic><topic>Motivation - drug effects</topic><topic>Nucleus Accumbens - drug effects</topic><topic>Nucleus Accumbens - secretion</topic><topic>Piperazines - pharmacology</topic><topic>Prefrontal Cortex - drug effects</topic><topic>Prefrontal Cortex - secretion</topic><topic>Rats</topic><topic>Receptor, Serotonin, 5-HT1A - metabolism</topic><topic>Receptor, Serotonin, 5-HT1B - metabolism</topic><topic>Reward</topic><topic>Serotonin 5-HT1 Receptor Agonists - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Korte, S Mechiel</creatorcontrib><creatorcontrib>Prins, Jolanda</creatorcontrib><creatorcontrib>Van den Bergh, Filip S</creatorcontrib><creatorcontrib>Oosting, Ronald S</creatorcontrib><creatorcontrib>Dupree, Rudy</creatorcontrib><creatorcontrib>Korte-Bouws, Gerdien A H</creatorcontrib><creatorcontrib>Westphal, Koen G C</creatorcontrib><creatorcontrib>Olivier, Berend</creatorcontrib><creatorcontrib>Denys, Damiaan A</creatorcontrib><creatorcontrib>Garland, Alexis</creatorcontrib><creatorcontrib>Güntürkün, Onur</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Korte, S Mechiel</au><au>Prins, Jolanda</au><au>Van den Bergh, Filip S</au><au>Oosting, Ronald S</au><au>Dupree, Rudy</au><au>Korte-Bouws, Gerdien A H</au><au>Westphal, Koen G C</au><au>Olivier, Berend</au><au>Denys, Damiaan A</au><au>Garland, Alexis</au><au>Güntürkün, Onur</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The 5-HT 1A/1B -receptor agonist eltoprazine increases both catecholamine release in the prefrontal cortex and dopamine release in the nucleus accumbens and decreases motivation for reward and "waiting" impulsivity, but increases "stopping" impulsivity</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2017-01-05</date><risdate>2017</risdate><volume>794</volume><spage>257</spage><pages>257-</pages><eissn>1879-0712</eissn><abstract>The 5-HT
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| ispartof | European journal of pharmacology, 2017-01, Vol.794, p.257 |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Animals Choice Behavior - drug effects Dopamine - secretion Impulsive Behavior - drug effects Male Motivation - drug effects Nucleus Accumbens - drug effects Nucleus Accumbens - secretion Piperazines - pharmacology Prefrontal Cortex - drug effects Prefrontal Cortex - secretion Rats Receptor, Serotonin, 5-HT1A - metabolism Receptor, Serotonin, 5-HT1B - metabolism Reward Serotonin 5-HT1 Receptor Agonists - pharmacology |
| title | The 5-HT 1A/1B -receptor agonist eltoprazine increases both catecholamine release in the prefrontal cortex and dopamine release in the nucleus accumbens and decreases motivation for reward and "waiting" impulsivity, but increases "stopping" impulsivity |
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