Loading…
Pharmacologic actions of subtype-selective and novel GABAergic ligands in rat lines with differential sensitivity to ethanol
Alcohol-nontolerant (ANT) rats, produced by selective breeding for high sensitivity to motor-impairing effects of ethanol, have a point mutation in the cerebellar γ-aminobutyric acid type A (GABA A) receptor α6 subunit, which has been proposed to underlie enhanced sensitivity to benzodiazepine agoni...
Saved in:
| Published in: | Pharmacology, biochemistry and behavior biochemistry and behavior, 1996-03, Vol.53 (3), p.723-730 |
|---|---|
| Main Authors: | , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c386t-48eb9683315b398736e612cc4504f550f061c71ce0128fc70b725bb5dffdf0e03 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c386t-48eb9683315b398736e612cc4504f550f061c71ce0128fc70b725bb5dffdf0e03 |
| container_end_page | 730 |
| container_issue | 3 |
| container_start_page | 723 |
| container_title | Pharmacology, biochemistry and behavior |
| container_volume | 53 |
| creator | Wong, Garry Sarviharju, Maija Toropainen, Maija Matecka, Dorota Korpi, Esa R. |
| description | Alcohol-nontolerant (ANT) rats, produced by selective breeding for high sensitivity to motor-impairing effects of ethanol, have a point mutation in the cerebellar γ-aminobutyric acid type A (GABA
A) receptor α6 subunit, which has been proposed to underlie enhanced sensitivity to benzodiazepine agonists as well. We compared ANT and alcohol-tolerant (AT) rats using behavioral and neurochemical methods to assess the significance of α6- and nonα6-containing GABA
A receptor subtypes. Motor performance in a tilting plane test was largely unaffected by a type I benzodiazepine receptor-preferring agonist, zolpidem [1–10 mg/kg, intraperitoneally (IP)], partial benzodiazepine agonists bretazenil and ZG-63 (both at 40 mg/kg, IP), and a novel broad-spectrum anticonvulsant loreclezole (40 mg/kg, IP) in both ANT and AT rats. In contrast, diazepam (10 mg/kg, IP) impaired performance of the ANT but not AT animals. These data, supported by results from brain regional autoradiography of [
3H]Ro15-4513 and membrane binding of [
3H]ZG-63 and [
35S]TBPS as influenced by these ligands, strongly suggest that only ligands with full agonist actions on mutant (ANT) but not wild-type (AT) α6-containing GABA
A receptors are able to produce motor impairment in the ANT rats. |
| doi_str_mv | 10.1016/0091-3057(95)02076-4 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_78432269</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>0091305795020764</els_id><sourcerecordid>78432269</sourcerecordid><originalsourceid>FETCH-LOGICAL-c386t-48eb9683315b398736e612cc4504f550f061c71ce0128fc70b725bb5dffdf0e03</originalsourceid><addsrcrecordid>eNp9kUGLFDEQhYMo67j6DxRyENFDa6W7k3RfhHHRVVjQg55DOl3ZiWSSMcmMDPjjTTvDHD0VVfXeo_KFkOcM3jJg4h3AyJoOuHw98jfQghRN_4Cs2CC7hjMpH5LVRfKYPMn5JwD0rZBX5GoYhBilXJE_3zY6bbWJPt47Q7UpLoZMo6V5P5XjDpuMHuv0gFSHmYZ4QE9v1x_WmBaDd_d1nKkLNOlS24CZ_nZlQ2dnLSYMxWlPM4bsaogrR1oixbLRIfqn5JHVPuOzc70mPz59_H7zubn7evvlZn3XmG4QpekHnEYxdB3jUzfW5wkUrDWm59BbzsGCYEYyg8DawRoJk2z5NPHZ2tkCQndNXp1ydyn-2mMuauuyQe91wLjPSg5917ZirML-JDQp5pzQql1yW52OioFaoKuFqFqIqpGrf9BVX20vzvn7aYvzxXSmXPcvz3udjfY26WBcvsg66Lnky5nvTzKsLA4Ok8rGYTA4u1S_QM3R_f-Ov-ZdnyA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>78432269</pqid></control><display><type>article</type><title>Pharmacologic actions of subtype-selective and novel GABAergic ligands in rat lines with differential sensitivity to ethanol</title><source>ScienceDirect Freedom Collection</source><creator>Wong, Garry ; Sarviharju, Maija ; Toropainen, Maija ; Matecka, Dorota ; Korpi, Esa R.</creator><creatorcontrib>Wong, Garry ; Sarviharju, Maija ; Toropainen, Maija ; Matecka, Dorota ; Korpi, Esa R.</creatorcontrib><description>Alcohol-nontolerant (ANT) rats, produced by selective breeding for high sensitivity to motor-impairing effects of ethanol, have a point mutation in the cerebellar γ-aminobutyric acid type A (GABA
A) receptor α6 subunit, which has been proposed to underlie enhanced sensitivity to benzodiazepine agonists as well. We compared ANT and alcohol-tolerant (AT) rats using behavioral and neurochemical methods to assess the significance of α6- and nonα6-containing GABA
A receptor subtypes. Motor performance in a tilting plane test was largely unaffected by a type I benzodiazepine receptor-preferring agonist, zolpidem [1–10 mg/kg, intraperitoneally (IP)], partial benzodiazepine agonists bretazenil and ZG-63 (both at 40 mg/kg, IP), and a novel broad-spectrum anticonvulsant loreclezole (40 mg/kg, IP) in both ANT and AT rats. In contrast, diazepam (10 mg/kg, IP) impaired performance of the ANT but not AT animals. These data, supported by results from brain regional autoradiography of [
3H]Ro15-4513 and membrane binding of [
3H]ZG-63 and [
35S]TBPS as influenced by these ligands, strongly suggest that only ligands with full agonist actions on mutant (ANT) but not wild-type (AT) α6-containing GABA
A receptors are able to produce motor impairment in the ANT rats.</description><identifier>ISSN: 0091-3057</identifier><identifier>EISSN: 1873-5177</identifier><identifier>DOI: 10.1016/0091-3057(95)02076-4</identifier><identifier>PMID: 8866977</identifier><identifier>CODEN: PBBHAU</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Alcohol sensitivity ; Alcoholism and acute alcohol poisoning ; Animals ; Autoradiography ; Benzodiazepine receptors ; Binding, Competitive ; Biological and medical sciences ; Bretazenil ; Diazepam - pharmacology ; Dose-Response Relationship, Drug ; Ethanol - pharmacology ; GABA A receptor subtypes ; gamma-Aminobutyric Acid - pharmacology ; Hypnotics and Sedatives - pharmacology ; Loreclezole ; Male ; Medical sciences ; Motor Activity - drug effects ; Pyridines - pharmacology ; Rats ; Selected rat lines ; Toxicology ; Triazoles - pharmacology ; ZG-63 ; Zolpidem</subject><ispartof>Pharmacology, biochemistry and behavior, 1996-03, Vol.53 (3), p.723-730</ispartof><rights>1996</rights><rights>1996 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-48eb9683315b398736e612cc4504f550f061c71ce0128fc70b725bb5dffdf0e03</citedby><cites>FETCH-LOGICAL-c386t-48eb9683315b398736e612cc4504f550f061c71ce0128fc70b725bb5dffdf0e03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3045750$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8866977$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wong, Garry</creatorcontrib><creatorcontrib>Sarviharju, Maija</creatorcontrib><creatorcontrib>Toropainen, Maija</creatorcontrib><creatorcontrib>Matecka, Dorota</creatorcontrib><creatorcontrib>Korpi, Esa R.</creatorcontrib><title>Pharmacologic actions of subtype-selective and novel GABAergic ligands in rat lines with differential sensitivity to ethanol</title><title>Pharmacology, biochemistry and behavior</title><addtitle>Pharmacol Biochem Behav</addtitle><description>Alcohol-nontolerant (ANT) rats, produced by selective breeding for high sensitivity to motor-impairing effects of ethanol, have a point mutation in the cerebellar γ-aminobutyric acid type A (GABA
A) receptor α6 subunit, which has been proposed to underlie enhanced sensitivity to benzodiazepine agonists as well. We compared ANT and alcohol-tolerant (AT) rats using behavioral and neurochemical methods to assess the significance of α6- and nonα6-containing GABA
A receptor subtypes. Motor performance in a tilting plane test was largely unaffected by a type I benzodiazepine receptor-preferring agonist, zolpidem [1–10 mg/kg, intraperitoneally (IP)], partial benzodiazepine agonists bretazenil and ZG-63 (both at 40 mg/kg, IP), and a novel broad-spectrum anticonvulsant loreclezole (40 mg/kg, IP) in both ANT and AT rats. In contrast, diazepam (10 mg/kg, IP) impaired performance of the ANT but not AT animals. These data, supported by results from brain regional autoradiography of [
3H]Ro15-4513 and membrane binding of [
3H]ZG-63 and [
35S]TBPS as influenced by these ligands, strongly suggest that only ligands with full agonist actions on mutant (ANT) but not wild-type (AT) α6-containing GABA
A receptors are able to produce motor impairment in the ANT rats.</description><subject>Alcohol sensitivity</subject><subject>Alcoholism and acute alcohol poisoning</subject><subject>Animals</subject><subject>Autoradiography</subject><subject>Benzodiazepine receptors</subject><subject>Binding, Competitive</subject><subject>Biological and medical sciences</subject><subject>Bretazenil</subject><subject>Diazepam - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Ethanol - pharmacology</subject><subject>GABA A receptor subtypes</subject><subject>gamma-Aminobutyric Acid - pharmacology</subject><subject>Hypnotics and Sedatives - pharmacology</subject><subject>Loreclezole</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Motor Activity - drug effects</subject><subject>Pyridines - pharmacology</subject><subject>Rats</subject><subject>Selected rat lines</subject><subject>Toxicology</subject><subject>Triazoles - pharmacology</subject><subject>ZG-63</subject><subject>Zolpidem</subject><issn>0091-3057</issn><issn>1873-5177</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><recordid>eNp9kUGLFDEQhYMo67j6DxRyENFDa6W7k3RfhHHRVVjQg55DOl3ZiWSSMcmMDPjjTTvDHD0VVfXeo_KFkOcM3jJg4h3AyJoOuHw98jfQghRN_4Cs2CC7hjMpH5LVRfKYPMn5JwD0rZBX5GoYhBilXJE_3zY6bbWJPt47Q7UpLoZMo6V5P5XjDpuMHuv0gFSHmYZ4QE9v1x_WmBaDd_d1nKkLNOlS24CZ_nZlQ2dnLSYMxWlPM4bsaogrR1oixbLRIfqn5JHVPuOzc70mPz59_H7zubn7evvlZn3XmG4QpekHnEYxdB3jUzfW5wkUrDWm59BbzsGCYEYyg8DawRoJk2z5NPHZ2tkCQndNXp1ydyn-2mMuauuyQe91wLjPSg5917ZirML-JDQp5pzQql1yW52OioFaoKuFqFqIqpGrf9BVX20vzvn7aYvzxXSmXPcvz3udjfY26WBcvsg66Lnky5nvTzKsLA4Ok8rGYTA4u1S_QM3R_f-Ov-ZdnyA</recordid><startdate>19960301</startdate><enddate>19960301</enddate><creator>Wong, Garry</creator><creator>Sarviharju, Maija</creator><creator>Toropainen, Maija</creator><creator>Matecka, Dorota</creator><creator>Korpi, Esa R.</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>7X8</scope></search><sort><creationdate>19960301</creationdate><title>Pharmacologic actions of subtype-selective and novel GABAergic ligands in rat lines with differential sensitivity to ethanol</title><author>Wong, Garry ; Sarviharju, Maija ; Toropainen, Maija ; Matecka, Dorota ; Korpi, Esa R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-48eb9683315b398736e612cc4504f550f061c71ce0128fc70b725bb5dffdf0e03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Alcohol sensitivity</topic><topic>Alcoholism and acute alcohol poisoning</topic><topic>Animals</topic><topic>Autoradiography</topic><topic>Benzodiazepine receptors</topic><topic>Binding, Competitive</topic><topic>Biological and medical sciences</topic><topic>Bretazenil</topic><topic>Diazepam - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Ethanol - pharmacology</topic><topic>GABA A receptor subtypes</topic><topic>gamma-Aminobutyric Acid - pharmacology</topic><topic>Hypnotics and Sedatives - pharmacology</topic><topic>Loreclezole</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Motor Activity - drug effects</topic><topic>Pyridines - pharmacology</topic><topic>Rats</topic><topic>Selected rat lines</topic><topic>Toxicology</topic><topic>Triazoles - pharmacology</topic><topic>ZG-63</topic><topic>Zolpidem</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wong, Garry</creatorcontrib><creatorcontrib>Sarviharju, Maija</creatorcontrib><creatorcontrib>Toropainen, Maija</creatorcontrib><creatorcontrib>Matecka, Dorota</creatorcontrib><creatorcontrib>Korpi, Esa R.</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>Pharmacology, biochemistry and behavior</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wong, Garry</au><au>Sarviharju, Maija</au><au>Toropainen, Maija</au><au>Matecka, Dorota</au><au>Korpi, Esa R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacologic actions of subtype-selective and novel GABAergic ligands in rat lines with differential sensitivity to ethanol</atitle><jtitle>Pharmacology, biochemistry and behavior</jtitle><addtitle>Pharmacol Biochem Behav</addtitle><date>1996-03-01</date><risdate>1996</risdate><volume>53</volume><issue>3</issue><spage>723</spage><epage>730</epage><pages>723-730</pages><issn>0091-3057</issn><eissn>1873-5177</eissn><coden>PBBHAU</coden><abstract>Alcohol-nontolerant (ANT) rats, produced by selective breeding for high sensitivity to motor-impairing effects of ethanol, have a point mutation in the cerebellar γ-aminobutyric acid type A (GABA
A) receptor α6 subunit, which has been proposed to underlie enhanced sensitivity to benzodiazepine agonists as well. We compared ANT and alcohol-tolerant (AT) rats using behavioral and neurochemical methods to assess the significance of α6- and nonα6-containing GABA
A receptor subtypes. Motor performance in a tilting plane test was largely unaffected by a type I benzodiazepine receptor-preferring agonist, zolpidem [1–10 mg/kg, intraperitoneally (IP)], partial benzodiazepine agonists bretazenil and ZG-63 (both at 40 mg/kg, IP), and a novel broad-spectrum anticonvulsant loreclezole (40 mg/kg, IP) in both ANT and AT rats. In contrast, diazepam (10 mg/kg, IP) impaired performance of the ANT but not AT animals. These data, supported by results from brain regional autoradiography of [
3H]Ro15-4513 and membrane binding of [
3H]ZG-63 and [
35S]TBPS as influenced by these ligands, strongly suggest that only ligands with full agonist actions on mutant (ANT) but not wild-type (AT) α6-containing GABA
A receptors are able to produce motor impairment in the ANT rats.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>8866977</pmid><doi>10.1016/0091-3057(95)02076-4</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0091-3057 |
| ispartof | Pharmacology, biochemistry and behavior, 1996-03, Vol.53 (3), p.723-730 |
| issn | 0091-3057 1873-5177 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_78432269 |
| source | ScienceDirect Freedom Collection |
| subjects | Alcohol sensitivity Alcoholism and acute alcohol poisoning Animals Autoradiography Benzodiazepine receptors Binding, Competitive Biological and medical sciences Bretazenil Diazepam - pharmacology Dose-Response Relationship, Drug Ethanol - pharmacology GABA A receptor subtypes gamma-Aminobutyric Acid - pharmacology Hypnotics and Sedatives - pharmacology Loreclezole Male Medical sciences Motor Activity - drug effects Pyridines - pharmacology Rats Selected rat lines Toxicology Triazoles - pharmacology ZG-63 Zolpidem |
| title | Pharmacologic actions of subtype-selective and novel GABAergic ligands in rat lines with differential sensitivity to ethanol |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T07%3A14%3A01IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Pharmacologic%20actions%20of%20subtype-selective%20and%20novel%20GABAergic%20ligands%20in%20rat%20lines%20with%20differential%20sensitivity%20to%20ethanol&rft.jtitle=Pharmacology,%20biochemistry%20and%20behavior&rft.au=Wong,%20Garry&rft.date=1996-03-01&rft.volume=53&rft.issue=3&rft.spage=723&rft.epage=730&rft.pages=723-730&rft.issn=0091-3057&rft.eissn=1873-5177&rft.coden=PBBHAU&rft_id=info:doi/10.1016/0091-3057(95)02076-4&rft_dat=%3Cproquest_cross%3E78432269%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c386t-48eb9683315b398736e612cc4504f550f061c71ce0128fc70b725bb5dffdf0e03%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=78432269&rft_id=info:pmid/8866977&rfr_iscdi=true |