Glutamate receptor antagonism in inferior colliculus attenuates elevated startle response of high anxiety diazepam-withdrawn rats
Abstract Rats segregated according to low (LA) or high (HA) anxiety levels have been used as an important tool in the study of fear and anxiety. Since the efficacy of an anxiolytic compound is a function of the animal's basal anxiety level, it is possible that chronic treatment with a benzodiaz...
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| Veröffentlicht in: | Neuroscience 2009-07, Vol.161 (3), p.707-717 |
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| creator | Cabral, A De Ross, J Castilho, V.M Brandão, M.L Nobre, M.J |
| description | Abstract Rats segregated according to low (LA) or high (HA) anxiety levels have been used as an important tool in the study of fear and anxiety. Since the efficacy of an anxiolytic compound is a function of the animal's basal anxiety level, it is possible that chronic treatment with a benzodiazepine (Bzp) affects LA and HA animals differently. Based on these assumptions, this study aimed to provide some additional information on the influence of acute, chronic (18 days) and withdrawal effects (48 h) from diazepam (10 mg/kg), in rats with LA or HA levels, on startle response amplitude. For this purpose, the elevated plus-maze (EPM) test was used. In addition, the role of glutamate receptors of the central nucleus of the inferior colliculus (cIC), the most important mesencephalic tectum integrative structure of the auditory pathways and a brain region that is linked to the processing of auditory information of aversive nature, was also evaluated. Our results showed that, contrary to the results obtained in LA rats, long-term treatment with diazepam promoted anxiolytic and aversive effects in HA animals that were tested under chronic effects or withdrawal from this drug, respectively. In addition, since Bzp withdrawal may function as an unconditioned stressor, the negative affective states observed in HA rats could be a by-product of GABA-glutamate imbalance in brain systems that modulate unconditioned fear and anxiety behaviors, since the blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and N-methyl- d -aspartate (NMDA) glutamate receptors in the cIC clearly reduced the aversion promoted by diazepam withdrawal. |
| doi_str_mv | 10.1016/j.neuroscience.2009.03.073 |
| format | Article |
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Since the efficacy of an anxiolytic compound is a function of the animal's basal anxiety level, it is possible that chronic treatment with a benzodiazepine (Bzp) affects LA and HA animals differently. Based on these assumptions, this study aimed to provide some additional information on the influence of acute, chronic (18 days) and withdrawal effects (48 h) from diazepam (10 mg/kg), in rats with LA or HA levels, on startle response amplitude. For this purpose, the elevated plus-maze (EPM) test was used. In addition, the role of glutamate receptors of the central nucleus of the inferior colliculus (cIC), the most important mesencephalic tectum integrative structure of the auditory pathways and a brain region that is linked to the processing of auditory information of aversive nature, was also evaluated. Our results showed that, contrary to the results obtained in LA rats, long-term treatment with diazepam promoted anxiolytic and aversive effects in HA animals that were tested under chronic effects or withdrawal from this drug, respectively. In addition, since Bzp withdrawal may function as an unconditioned stressor, the negative affective states observed in HA rats could be a by-product of GABA-glutamate imbalance in brain systems that modulate unconditioned fear and anxiety behaviors, since the blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and N-methyl- d -aspartate (NMDA) glutamate receptors in the cIC clearly reduced the aversion promoted by diazepam withdrawal.</description><identifier>ISSN: 0306-4522</identifier><identifier>EISSN: 1873-7544</identifier><identifier>DOI: 10.1016/j.neuroscience.2009.03.073</identifier><identifier>PMID: 19348870</identifier><identifier>CODEN: NRSCDN</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ltd</publisher><subject>Acoustic Stimulation ; Animals ; Anti-Anxiety Agents - administration & dosage ; Anti-Anxiety Agents - adverse effects ; anxiety ; Anxiety - psychology ; Biological and medical sciences ; Diazepam - administration & dosage ; Diazepam - adverse effects ; diazepam withdrawal ; Ear and associated structures. 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Psychology ; glutamate ; Inferior Colliculi - drug effects ; Inferior Colliculi - physiology ; inferior colliculus ; Male ; Maze Learning - drug effects ; Maze Learning - physiology ; Neurology ; Rats ; Rats, Wistar ; Receptors, AMPA - antagonists & inhibitors ; Receptors, Glutamate - metabolism ; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors ; Reflex, Startle - drug effects ; Reflex, Startle - physiology ; Species Specificity ; startle response ; Substance Withdrawal Syndrome ; Ultrasonics ; Vertebrates: nervous system and sense organs ; Vocalization, Animal - drug effects ; Vocalization, Animal - physiology</subject><ispartof>Neuroscience, 2009-07, Vol.161 (3), p.707-717</ispartof><rights>IBRO</rights><rights>2009 IBRO</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c560t-67801de63251f7ebe415bd4586d71fc4c6f851919f9e705a158c1dd859763b693</citedby><cites>FETCH-LOGICAL-c560t-67801de63251f7ebe415bd4586d71fc4c6f851919f9e705a158c1dd859763b693</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.neuroscience.2009.03.073$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3541,27915,27916,45986</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21589027$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19348870$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cabral, A</creatorcontrib><creatorcontrib>De Ross, J</creatorcontrib><creatorcontrib>Castilho, V.M</creatorcontrib><creatorcontrib>Brandão, M.L</creatorcontrib><creatorcontrib>Nobre, M.J</creatorcontrib><title>Glutamate receptor antagonism in inferior colliculus attenuates elevated startle response of high anxiety diazepam-withdrawn rats</title><title>Neuroscience</title><addtitle>Neuroscience</addtitle><description>Abstract Rats segregated according to low (LA) or high (HA) anxiety levels have been used as an important tool in the study of fear and anxiety. Since the efficacy of an anxiolytic compound is a function of the animal's basal anxiety level, it is possible that chronic treatment with a benzodiazepine (Bzp) affects LA and HA animals differently. Based on these assumptions, this study aimed to provide some additional information on the influence of acute, chronic (18 days) and withdrawal effects (48 h) from diazepam (10 mg/kg), in rats with LA or HA levels, on startle response amplitude. For this purpose, the elevated plus-maze (EPM) test was used. In addition, the role of glutamate receptors of the central nucleus of the inferior colliculus (cIC), the most important mesencephalic tectum integrative structure of the auditory pathways and a brain region that is linked to the processing of auditory information of aversive nature, was also evaluated. Our results showed that, contrary to the results obtained in LA rats, long-term treatment with diazepam promoted anxiolytic and aversive effects in HA animals that were tested under chronic effects or withdrawal from this drug, respectively. In addition, since Bzp withdrawal may function as an unconditioned stressor, the negative affective states observed in HA rats could be a by-product of GABA-glutamate imbalance in brain systems that modulate unconditioned fear and anxiety behaviors, since the blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and N-methyl- d -aspartate (NMDA) glutamate receptors in the cIC clearly reduced the aversion promoted by diazepam withdrawal.</description><subject>Acoustic Stimulation</subject><subject>Animals</subject><subject>Anti-Anxiety Agents - administration & dosage</subject><subject>Anti-Anxiety Agents - adverse effects</subject><subject>anxiety</subject><subject>Anxiety - psychology</subject><subject>Biological and medical sciences</subject><subject>Diazepam - administration & dosage</subject><subject>Diazepam - adverse effects</subject><subject>diazepam withdrawal</subject><subject>Ear and associated structures. Auditory pathways and centers. Hearing. 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Psychology</subject><subject>glutamate</subject><subject>Inferior Colliculi - drug effects</subject><subject>Inferior Colliculi - physiology</subject><subject>inferior colliculus</subject><subject>Male</subject><subject>Maze Learning - drug effects</subject><subject>Maze Learning - physiology</subject><subject>Neurology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptors, AMPA - antagonists & inhibitors</subject><subject>Receptors, Glutamate - metabolism</subject><subject>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</subject><subject>Reflex, Startle - drug effects</subject><subject>Reflex, Startle - physiology</subject><subject>Species Specificity</subject><subject>startle response</subject><subject>Substance Withdrawal Syndrome</subject><subject>Ultrasonics</subject><subject>Vertebrates: nervous system and sense organs</subject><subject>Vocalization, Animal - drug effects</subject><subject>Vocalization, Animal - physiology</subject><issn>0306-4522</issn><issn>1873-7544</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNklGP1CAUhYnRuOPqXzDERN9aoRRofTDZrLqabOKD-kwYuN1hpHQEuuv45j-XZho1PklIIOS755JzLkLPKKkpoeLlvg4wxykZB8FA3RDS14TVRLJ7aEM7ySrJ2_Y-2hBGRNXypjlDj1Lak7J4yx6iM9qztusk2aCfV37OetQZcAQDhzxFrEPWN1NwacQulD1AdOXZTN47M_s5YZ0zhLkUJQwebsvF4pR1zH6RSYcpJMDTgHfuZlfkvjvIR2yd_gEHPVZ3Lu9s1HcBR53TY_Rg0D7Bk_U8R1_evf18-b66_nj14fLiujJckFwJ2RFqQbCG00HCFlrKt7blnbCSDqY1Yug47Wk_9CAJ15R3hlrb8V4KthU9O0cvTrqHOH2bIWU1umTAex1gmpNqiKCU0QV8dQJN8ThFGNQhulHHo6JELQGovfo7ALUEoAhTJYBS_HTtMm9HsH9KV8cL8HwFdDLaD1EH49Jvrin_7kkjC_fmxEHx5NZBVGs760pQWdnJ_d9_Xv8jY7wLrnT-CkdI-2mOobiuqEqNIurTMjLLxJC-zAoTjP0CXNjDSA</recordid><startdate>20090707</startdate><enddate>20090707</enddate><creator>Cabral, A</creator><creator>De Ross, J</creator><creator>Castilho, V.M</creator><creator>Brandão, M.L</creator><creator>Nobre, M.J</creator><general>Elsevier Ltd</general><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>7QG</scope><scope>7TK</scope></search><sort><creationdate>20090707</creationdate><title>Glutamate receptor antagonism in inferior colliculus attenuates elevated startle response of high anxiety diazepam-withdrawn rats</title><author>Cabral, A ; De Ross, J ; Castilho, V.M ; Brandão, M.L ; Nobre, M.J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c560t-67801de63251f7ebe415bd4586d71fc4c6f851919f9e705a158c1dd859763b693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Acoustic Stimulation</topic><topic>Animals</topic><topic>Anti-Anxiety Agents - administration & dosage</topic><topic>Anti-Anxiety Agents - adverse effects</topic><topic>anxiety</topic><topic>Anxiety - psychology</topic><topic>Biological and medical sciences</topic><topic>Diazepam - administration & dosage</topic><topic>Diazepam - adverse effects</topic><topic>diazepam withdrawal</topic><topic>Ear and associated structures. Auditory pathways and centers. Hearing. Vocal organ. Phonation. Sound production. Echolocation</topic><topic>elevated-plus-maze</topic><topic>Evoked Potentials, Auditory - drug effects</topic><topic>Excitatory Amino Acid Antagonists - administration & dosage</topic><topic>Fundamental and applied biological sciences. 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Our results showed that, contrary to the results obtained in LA rats, long-term treatment with diazepam promoted anxiolytic and aversive effects in HA animals that were tested under chronic effects or withdrawal from this drug, respectively. In addition, since Bzp withdrawal may function as an unconditioned stressor, the negative affective states observed in HA rats could be a by-product of GABA-glutamate imbalance in brain systems that modulate unconditioned fear and anxiety behaviors, since the blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and N-methyl- d -aspartate (NMDA) glutamate receptors in the cIC clearly reduced the aversion promoted by diazepam withdrawal.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>19348870</pmid><doi>10.1016/j.neuroscience.2009.03.073</doi><tpages>11</tpages></addata></record> |
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| subjects | Acoustic Stimulation Animals Anti-Anxiety Agents - administration & dosage Anti-Anxiety Agents - adverse effects anxiety Anxiety - psychology Biological and medical sciences Diazepam - administration & dosage Diazepam - adverse effects diazepam withdrawal Ear and associated structures. Auditory pathways and centers. Hearing. Vocal organ. Phonation. Sound production. Echolocation elevated-plus-maze Evoked Potentials, Auditory - drug effects Excitatory Amino Acid Antagonists - administration & dosage Fundamental and applied biological sciences. Psychology glutamate Inferior Colliculi - drug effects Inferior Colliculi - physiology inferior colliculus Male Maze Learning - drug effects Maze Learning - physiology Neurology Rats Rats, Wistar Receptors, AMPA - antagonists & inhibitors Receptors, Glutamate - metabolism Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors Reflex, Startle - drug effects Reflex, Startle - physiology Species Specificity startle response Substance Withdrawal Syndrome Ultrasonics Vertebrates: nervous system and sense organs Vocalization, Animal - drug effects Vocalization, Animal - physiology |
| title | Glutamate receptor antagonism in inferior colliculus attenuates elevated startle response of high anxiety diazepam-withdrawn rats |
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