Effects of the serotonin 5-HT2A and 5-HT2C receptor ligands on the discriminative stimulus effects of nicotine in rats
The present study tested the hypothesis that serotonergic (5-HT) 5-HT2A or 5-HT2C receptors or their pharmacological stimulation modulated the discriminative stimulus effects of nicotine in male Wistar rats. To this end the selective 5-HT2A receptor antagonist R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-...
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| description | The present study tested the hypothesis that serotonergic (5-HT) 5-HT2A or 5-HT2C receptors or their pharmacological stimulation modulated the discriminative stimulus effects of nicotine in male Wistar rats. To this end the selective 5-HT2A receptor antagonist R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol (M100,907; 0.5-1 mg/kg, i.p.), the functional 5-HT2A receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI; 0.1-1 mg/kg, s.c.), the selective 5-HT2C receptor antagonist 6-chloro-5-methyl-1-{[2-(2-methylpyrid-3-yloxy)pyrid-5-yl]carbamoyl}indoline (SB 242,084; 0.25-1 mg/kg, i.p.) and the 5-HT2C receptor agonists (S)-2-chloro-5-fluoro-indol-1-yl)-1-methylethylamine fumarate (Ro 60-0175; 0.3-1 mg/kg, s.c.) and (7bR, 10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7,1hi]indole (WAY 163,909; 0.75-1.5 mg/kg, i.p.) were used. Additionally, the effects of the selective alpha4beta2 nicotinic acetylcholine receptor subtype agonist 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5-IA; 0.01 mg/kg, s.c.) were investigated. In rats trained to discriminate (-)-nicotine (0.4 mg/kg, s.c.) from saline in a two-lever, water-reinforced fixed ratio 10 task, substitutions were not observed with 5-HT2 receptor ligands ( |
| doi_str_mv | 10.1016/j.ejphar.2007.05.067 |
| format | Article |
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To this end the selective 5-HT2A receptor antagonist R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol (M100,907; 0.5-1 mg/kg, i.p.), the functional 5-HT2A receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI; 0.1-1 mg/kg, s.c.), the selective 5-HT2C receptor antagonist 6-chloro-5-methyl-1-{[2-(2-methylpyrid-3-yloxy)pyrid-5-yl]carbamoyl}indoline (SB 242,084; 0.25-1 mg/kg, i.p.) and the 5-HT2C receptor agonists (S)-2-chloro-5-fluoro-indol-1-yl)-1-methylethylamine fumarate (Ro 60-0175; 0.3-1 mg/kg, s.c.) and (7bR, 10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7,1hi]indole (WAY 163,909; 0.75-1.5 mg/kg, i.p.) were used. Additionally, the effects of the selective alpha4beta2 nicotinic acetylcholine receptor subtype agonist 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5-IA; 0.01 mg/kg, s.c.) were investigated. In rats trained to discriminate (-)-nicotine (0.4 mg/kg, s.c.) from saline in a two-lever, water-reinforced fixed ratio 10 task, substitutions were not observed with 5-HT2 receptor ligands (<32% nicotine-lever responding), conversely 5-IA induced a full substitution (100% nicotine-lever responding). In combination studies, fixed doses of M100,907 (0.5-1 mg/kg) or SB 242,084 (0.25-1 mg/kg) did not alter the dose-response curve of nicotine, while DOI (0.3 mg/kg), Ro 60-0175 (1 mg/kg) and WAY 163,909 (1 and 1.5 mg/kg) attenuated the discriminative stimulus effects of nicotine. The decrease in the expression of the discriminative stimulus effects of nicotine produced by DOI was blocked by M100,907 (1 mg/kg), but not by SB 242,084 (1 mg/kg), while that evoked by Ro 60-0175 or WAY 163,909 was blocked by SB 242,084 (1 mg/kg), but not by M100,907 (1 mg/kg). Further studies showed that DOI (0.3 mg/kg) and Ro 60-0175 (1 mg/kg), but not WAY 163,909 (1.5 mg/kg) blocked full substitution of 5-IA (0.01 mg/kg) for nicotine. Our pharmacological analyses indicate that tonic activation of 5-HT2A or 5-HT2C receptors is not required for subjective effects of nicotine, however these receptors appear to have inhibitory influence on nicotine cue, since pharmacological stimulation of either receptor attenuates the discriminative stimulus effects of nicotine.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2007.05.067</identifier><identifier>PMID: 17617403</identifier><identifier>CODEN: EJPHAZ</identifier><language>eng</language><publisher>Amsterdam: Elsevier</publisher><subject>Aminopyridines - pharmacology ; Amphetamines - pharmacology ; Animals ; Azepines - pharmacology ; Azetidines - pharmacology ; Behavior, Animal - drug effects ; Biological and medical sciences ; Brain - drug effects ; Brain - metabolism ; Discrimination (Psychology) - drug effects ; Dose-Response Relationship, Drug ; Ethylamines - pharmacology ; Fluorobenzenes - pharmacology ; Indoles - pharmacology ; Ligands ; Male ; Medical sciences ; Nicotine - pharmacology ; Nicotinic Agonists - pharmacology ; Pharmacology. Drug treatments ; Piperidines - pharmacology ; Pyridines - pharmacology ; Rats ; Rats, Wistar ; Receptor, Serotonin, 5-HT2A - metabolism ; Receptor, Serotonin, 5-HT2C - metabolism ; Receptors, Nicotinic - drug effects ; Receptors, Nicotinic - metabolism ; Serotonin 5-HT2 Receptor Agonists ; Serotonin Antagonists - pharmacology ; Serotonin Receptor Agonists - pharmacology</subject><ispartof>European journal of pharmacology, 2007-10, Vol.571 (2-3), p.156-165</ispartof><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c335t-321227ed3d15857a9d4e666b82d20f11f20aa988fdf0aabd292f964bab4ac4893</citedby><cites>FETCH-LOGICAL-c335t-321227ed3d15857a9d4e666b82d20f11f20aa988fdf0aabd292f964bab4ac4893</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19086166$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17617403$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ZANIEWSKA, Magdalena</creatorcontrib><creatorcontrib>MCCREARY, Andrew C</creatorcontrib><creatorcontrib>PRZEGALINSKI, Edmund</creatorcontrib><creatorcontrib>FILIP, Malgorzata</creatorcontrib><title>Effects of the serotonin 5-HT2A and 5-HT2C receptor ligands on the discriminative stimulus effects of nicotine in rats</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>The present study tested the hypothesis that serotonergic (5-HT) 5-HT2A or 5-HT2C receptors or their pharmacological stimulation modulated the discriminative stimulus effects of nicotine in male Wistar rats. To this end the selective 5-HT2A receptor antagonist R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol (M100,907; 0.5-1 mg/kg, i.p.), the functional 5-HT2A receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI; 0.1-1 mg/kg, s.c.), the selective 5-HT2C receptor antagonist 6-chloro-5-methyl-1-{[2-(2-methylpyrid-3-yloxy)pyrid-5-yl]carbamoyl}indoline (SB 242,084; 0.25-1 mg/kg, i.p.) and the 5-HT2C receptor agonists (S)-2-chloro-5-fluoro-indol-1-yl)-1-methylethylamine fumarate (Ro 60-0175; 0.3-1 mg/kg, s.c.) and (7bR, 10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7,1hi]indole (WAY 163,909; 0.75-1.5 mg/kg, i.p.) were used. Additionally, the effects of the selective alpha4beta2 nicotinic acetylcholine receptor subtype agonist 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5-IA; 0.01 mg/kg, s.c.) were investigated. In rats trained to discriminate (-)-nicotine (0.4 mg/kg, s.c.) from saline in a two-lever, water-reinforced fixed ratio 10 task, substitutions were not observed with 5-HT2 receptor ligands (<32% nicotine-lever responding), conversely 5-IA induced a full substitution (100% nicotine-lever responding). In combination studies, fixed doses of M100,907 (0.5-1 mg/kg) or SB 242,084 (0.25-1 mg/kg) did not alter the dose-response curve of nicotine, while DOI (0.3 mg/kg), Ro 60-0175 (1 mg/kg) and WAY 163,909 (1 and 1.5 mg/kg) attenuated the discriminative stimulus effects of nicotine. The decrease in the expression of the discriminative stimulus effects of nicotine produced by DOI was blocked by M100,907 (1 mg/kg), but not by SB 242,084 (1 mg/kg), while that evoked by Ro 60-0175 or WAY 163,909 was blocked by SB 242,084 (1 mg/kg), but not by M100,907 (1 mg/kg). Further studies showed that DOI (0.3 mg/kg) and Ro 60-0175 (1 mg/kg), but not WAY 163,909 (1.5 mg/kg) blocked full substitution of 5-IA (0.01 mg/kg) for nicotine. Our pharmacological analyses indicate that tonic activation of 5-HT2A or 5-HT2C receptors is not required for subjective effects of nicotine, however these receptors appear to have inhibitory influence on nicotine cue, since pharmacological stimulation of either receptor attenuates the discriminative stimulus effects of nicotine.</description><subject>Aminopyridines - pharmacology</subject><subject>Amphetamines - pharmacology</subject><subject>Animals</subject><subject>Azepines - pharmacology</subject><subject>Azetidines - pharmacology</subject><subject>Behavior, Animal - drug effects</subject><subject>Biological and medical sciences</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Discrimination (Psychology) - drug effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>Ethylamines - pharmacology</subject><subject>Fluorobenzenes - pharmacology</subject><subject>Indoles - pharmacology</subject><subject>Ligands</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Nicotine - pharmacology</subject><subject>Nicotinic Agonists - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Piperidines - pharmacology</subject><subject>Pyridines - pharmacology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptor, Serotonin, 5-HT2A - metabolism</subject><subject>Receptor, Serotonin, 5-HT2C - metabolism</subject><subject>Receptors, Nicotinic - drug effects</subject><subject>Receptors, Nicotinic - metabolism</subject><subject>Serotonin 5-HT2 Receptor Agonists</subject><subject>Serotonin Antagonists - pharmacology</subject><subject>Serotonin Receptor Agonists - pharmacology</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkM1KJDEUhcPgMPaobyCSje6qvEmlkspSGn8GBDfOOqTyM6apTrVJSvDtjdMNvcolfOfj3oPQJYGWAOG3m9Ztdm86tRRAtNC3wMUPtCKDkA0IQk_QCoCwhkopT9HvnDcA0Eva_0KnRHAiGHQr9HHvvTMl49nj8uZwdmkucwwR983TK73DOtr9uMbJGbcrc8JT-Fe_ayb-z9iQTQrbEHUJH1VRwnaZlozdUR2DmUuIDldx0iWfo59eT9ldHN4z9Pfh_nX91Dy_PP5Z3z03puv60nSUUCqc7Szph15oaZnjnI8DtRQ8IZ6C1nIYvPV1GC2V1EvORj0ybdgguzN0s_fu0vy-uFzUti7rpklHNy9Z8YEKwpioINuDJs05J-fVrp6k06cioL77Vhu171t9962gV7XvGrs6-Jdx6-wxdCi4AtcHQGejJ590NCEfOQkDJ5x3XwiziwU</recordid><startdate>20071001</startdate><enddate>20071001</enddate><creator>ZANIEWSKA, Magdalena</creator><creator>MCCREARY, Andrew C</creator><creator>PRZEGALINSKI, Edmund</creator><creator>FILIP, Malgorzata</creator><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>7X8</scope></search><sort><creationdate>20071001</creationdate><title>Effects of the serotonin 5-HT2A and 5-HT2C receptor ligands on the discriminative stimulus effects of nicotine in rats</title><author>ZANIEWSKA, Magdalena ; MCCREARY, Andrew C ; PRZEGALINSKI, Edmund ; FILIP, Malgorzata</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c335t-321227ed3d15857a9d4e666b82d20f11f20aa988fdf0aabd292f964bab4ac4893</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Aminopyridines - pharmacology</topic><topic>Amphetamines - pharmacology</topic><topic>Animals</topic><topic>Azepines - pharmacology</topic><topic>Azetidines - pharmacology</topic><topic>Behavior, Animal - drug effects</topic><topic>Biological and medical sciences</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>Discrimination (Psychology) - drug effects</topic><topic>Dose-Response Relationship, Drug</topic><topic>Ethylamines - pharmacology</topic><topic>Fluorobenzenes - pharmacology</topic><topic>Indoles - pharmacology</topic><topic>Ligands</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Nicotine - pharmacology</topic><topic>Nicotinic Agonists - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Piperidines - pharmacology</topic><topic>Pyridines - pharmacology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptor, Serotonin, 5-HT2A - metabolism</topic><topic>Receptor, Serotonin, 5-HT2C - metabolism</topic><topic>Receptors, Nicotinic - drug effects</topic><topic>Receptors, Nicotinic - metabolism</topic><topic>Serotonin 5-HT2 Receptor Agonists</topic><topic>Serotonin Antagonists - pharmacology</topic><topic>Serotonin Receptor Agonists - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ZANIEWSKA, Magdalena</creatorcontrib><creatorcontrib>MCCREARY, Andrew C</creatorcontrib><creatorcontrib>PRZEGALINSKI, Edmund</creatorcontrib><creatorcontrib>FILIP, Malgorzata</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>MEDLINE - Academic</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ZANIEWSKA, Magdalena</au><au>MCCREARY, Andrew C</au><au>PRZEGALINSKI, Edmund</au><au>FILIP, Malgorzata</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of the serotonin 5-HT2A and 5-HT2C receptor ligands on the discriminative stimulus effects of nicotine in rats</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2007-10-01</date><risdate>2007</risdate><volume>571</volume><issue>2-3</issue><spage>156</spage><epage>165</epage><pages>156-165</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract>The present study tested the hypothesis that serotonergic (5-HT) 5-HT2A or 5-HT2C receptors or their pharmacological stimulation modulated the discriminative stimulus effects of nicotine in male Wistar rats. To this end the selective 5-HT2A receptor antagonist R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol (M100,907; 0.5-1 mg/kg, i.p.), the functional 5-HT2A receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI; 0.1-1 mg/kg, s.c.), the selective 5-HT2C receptor antagonist 6-chloro-5-methyl-1-{[2-(2-methylpyrid-3-yloxy)pyrid-5-yl]carbamoyl}indoline (SB 242,084; 0.25-1 mg/kg, i.p.) and the 5-HT2C receptor agonists (S)-2-chloro-5-fluoro-indol-1-yl)-1-methylethylamine fumarate (Ro 60-0175; 0.3-1 mg/kg, s.c.) and (7bR, 10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7,1hi]indole (WAY 163,909; 0.75-1.5 mg/kg, i.p.) were used. Additionally, the effects of the selective alpha4beta2 nicotinic acetylcholine receptor subtype agonist 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5-IA; 0.01 mg/kg, s.c.) were investigated. In rats trained to discriminate (-)-nicotine (0.4 mg/kg, s.c.) from saline in a two-lever, water-reinforced fixed ratio 10 task, substitutions were not observed with 5-HT2 receptor ligands (<32% nicotine-lever responding), conversely 5-IA induced a full substitution (100% nicotine-lever responding). In combination studies, fixed doses of M100,907 (0.5-1 mg/kg) or SB 242,084 (0.25-1 mg/kg) did not alter the dose-response curve of nicotine, while DOI (0.3 mg/kg), Ro 60-0175 (1 mg/kg) and WAY 163,909 (1 and 1.5 mg/kg) attenuated the discriminative stimulus effects of nicotine. The decrease in the expression of the discriminative stimulus effects of nicotine produced by DOI was blocked by M100,907 (1 mg/kg), but not by SB 242,084 (1 mg/kg), while that evoked by Ro 60-0175 or WAY 163,909 was blocked by SB 242,084 (1 mg/kg), but not by M100,907 (1 mg/kg). Further studies showed that DOI (0.3 mg/kg) and Ro 60-0175 (1 mg/kg), but not WAY 163,909 (1.5 mg/kg) blocked full substitution of 5-IA (0.01 mg/kg) for nicotine. Our pharmacological analyses indicate that tonic activation of 5-HT2A or 5-HT2C receptors is not required for subjective effects of nicotine, however these receptors appear to have inhibitory influence on nicotine cue, since pharmacological stimulation of either receptor attenuates the discriminative stimulus effects of nicotine.</abstract><cop>Amsterdam</cop><pub>Elsevier</pub><pmid>17617403</pmid><doi>10.1016/j.ejphar.2007.05.067</doi><tpages>10</tpages></addata></record> |
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| ispartof | European journal of pharmacology, 2007-10, Vol.571 (2-3), p.156-165 |
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| subjects | Aminopyridines - pharmacology Amphetamines - pharmacology Animals Azepines - pharmacology Azetidines - pharmacology Behavior, Animal - drug effects Biological and medical sciences Brain - drug effects Brain - metabolism Discrimination (Psychology) - drug effects Dose-Response Relationship, Drug Ethylamines - pharmacology Fluorobenzenes - pharmacology Indoles - pharmacology Ligands Male Medical sciences Nicotine - pharmacology Nicotinic Agonists - pharmacology Pharmacology. Drug treatments Piperidines - pharmacology Pyridines - pharmacology Rats Rats, Wistar Receptor, Serotonin, 5-HT2A - metabolism Receptor, Serotonin, 5-HT2C - metabolism Receptors, Nicotinic - drug effects Receptors, Nicotinic - metabolism Serotonin 5-HT2 Receptor Agonists Serotonin Antagonists - pharmacology Serotonin Receptor Agonists - pharmacology |
| title | Effects of the serotonin 5-HT2A and 5-HT2C receptor ligands on the discriminative stimulus effects of nicotine in rats |
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