Effect of acute and chronic administration of buspirone on serotonin and benzodiazepine receptor subtypes in the rat brain: An autoradiographic study
The affinity of buspirone and its main metabolite 1-(2-pyrimidinyl)piperazine (PmP) for serotonin 1 (5-HT 1) and benzodiazepine receptors was first evaluated by computerized receptor autoradiography. The results confirmed that buspirone is a selective 5-HT 1A ligand, since it inhibited the binding o...
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| Veröffentlicht in: | Neuropharmacology 1991-04, Vol.30 (4), p.313-321 |
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| description | The affinity of buspirone and its main metabolite 1-(2-pyrimidinyl)piperazine (PmP) for serotonin
1 (5-HT
1) and benzodiazepine receptors was first evaluated by computerized receptor autoradiography. The results confirmed that buspirone is a selective 5-HT
1A ligand, since it inhibited the binding of [
3H]5-HT with lower IC
50 values (about 100 nM) in regions of the brain of the rat where this receptor subtype is predominant (such as hippocampal areas). Larger IC
50 values than 3 μM were found in areas of the brain richer in 5-HT
1 receptors, other than the 5-HT
1A subtype (e.g. striatum, substantia nigra and the ventricles). The PmP was not selective, inhibiting the binding of [
3H]5-HT with similar affinity (about 4–10 μM) in all the regions of the brain examined. Neither buspirone nor PmP, up to 100 μM, were active on benzodiazepine receptors.
The autoradiographic technique was therefore used to evaluate the effects of acute (10 mg/kg, p.o., 1 hr before killing) and chronic (10 mg/kg, i.p., twice a day for 21 days, 24 hr washout) treatment with buspirone in male rats. Acute treatment reduced the binding of [
3H]5-HT in all the regions of the brain studied, including those with low levels of 5-HT
1A receptors, indicating the occupancy of 5-HT
1 receptors by either buspirone or its metabolite. The binding of [
3H]flunitrazepam was decreased (16%) only in the substantia nigra. The benzodiazepine/GABA receptors present in the substantia nigra, also undergo adaptive changes after chronic treatment with buspirone: only in this region was binding to benzodiazepine receptors increased by 41% (mainly due to type I receptors) and GABA partly lost its enhancing efficacy.
Moreover, chronic administration of buspirone significantly reduced (21%) the binding of [
3H]5-HT to 5-HT
1A receptors in the dorsal raphe, whereas a significant increase in binding of [
3H]5-HT (32%) was found in the substantia nigra, which was unrelated to any modification of 5-HT
1A receptors. No significant changes were evident in the other regions of the brain. |
| doi_str_mv | 10.1016/0028-3908(91)90055-G |
| format | Article |
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1 (5-HT
1) and benzodiazepine receptors was first evaluated by computerized receptor autoradiography. The results confirmed that buspirone is a selective 5-HT
1A ligand, since it inhibited the binding of [
3H]5-HT with lower IC
50 values (about 100 nM) in regions of the brain of the rat where this receptor subtype is predominant (such as hippocampal areas). Larger IC
50 values than 3 μM were found in areas of the brain richer in 5-HT
1 receptors, other than the 5-HT
1A subtype (e.g. striatum, substantia nigra and the ventricles). The PmP was not selective, inhibiting the binding of [
3H]5-HT with similar affinity (about 4–10 μM) in all the regions of the brain examined. Neither buspirone nor PmP, up to 100 μM, were active on benzodiazepine receptors.
The autoradiographic technique was therefore used to evaluate the effects of acute (10 mg/kg, p.o., 1 hr before killing) and chronic (10 mg/kg, i.p., twice a day for 21 days, 24 hr washout) treatment with buspirone in male rats. Acute treatment reduced the binding of [
3H]5-HT in all the regions of the brain studied, including those with low levels of 5-HT
1A receptors, indicating the occupancy of 5-HT
1 receptors by either buspirone or its metabolite. The binding of [
3H]flunitrazepam was decreased (16%) only in the substantia nigra. The benzodiazepine/GABA receptors present in the substantia nigra, also undergo adaptive changes after chronic treatment with buspirone: only in this region was binding to benzodiazepine receptors increased by 41% (mainly due to type I receptors) and GABA partly lost its enhancing efficacy.
Moreover, chronic administration of buspirone significantly reduced (21%) the binding of [
3H]5-HT to 5-HT
1A receptors in the dorsal raphe, whereas a significant increase in binding of [
3H]5-HT (32%) was found in the substantia nigra, which was unrelated to any modification of 5-HT
1A receptors. No significant changes were evident in the other regions of the brain.</description><identifier>ISSN: 0028-3908</identifier><identifier>EISSN: 1873-7064</identifier><identifier>DOI: 10.1016/0028-3908(91)90055-G</identifier><identifier>PMID: 1649418</identifier><identifier>CODEN: NEPHBW</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Animals ; anxiolytic drugs ; Autoradiography ; benzodiazepine receptors ; Biological and medical sciences ; Brain - metabolism ; buspirone ; Buspirone - administration & dosage ; Buspirone - pharmacology ; Flunitrazepam - metabolism ; In Vitro Techniques ; Male ; Medical sciences ; Neuropharmacology ; Pharmacology. Drug treatments ; Psycholeptics: tranquillizer, neuroleptic ; Psychology. Psychoanalysis. Psychiatry ; Psychopharmacology ; Radioligand Assay ; Rats ; Receptors, GABA-A - drug effects ; Receptors, GABA-A - metabolism ; Receptors, Serotonin - metabolism ; Serotonin Antagonists ; serotonin receptors ; Time Factors</subject><ispartof>Neuropharmacology, 1991-04, Vol.30 (4), p.313-321</ispartof><rights>1991</rights><rights>1991 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c449t-abe75bc337b68d8250b7885516f78036c804ab38334399f769fb6cf5187f19a23</citedby><cites>FETCH-LOGICAL-c449t-abe75bc337b68d8250b7885516f78036c804ab38334399f769fb6cf5187f19a23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/0028-3908(91)90055-G$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19705588$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1649418$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gobbi, M.</creatorcontrib><creatorcontrib>Cavanus, S.</creatorcontrib><creatorcontrib>Miari, A.</creatorcontrib><creatorcontrib>Mennini, T.</creatorcontrib><title>Effect of acute and chronic administration of buspirone on serotonin and benzodiazepine receptor subtypes in the rat brain: An autoradiographic study</title><title>Neuropharmacology</title><addtitle>Neuropharmacology</addtitle><description>The affinity of buspirone and its main metabolite 1-(2-pyrimidinyl)piperazine (PmP) for serotonin
1 (5-HT
1) and benzodiazepine receptors was first evaluated by computerized receptor autoradiography. The results confirmed that buspirone is a selective 5-HT
1A ligand, since it inhibited the binding of [
3H]5-HT with lower IC
50 values (about 100 nM) in regions of the brain of the rat where this receptor subtype is predominant (such as hippocampal areas). Larger IC
50 values than 3 μM were found in areas of the brain richer in 5-HT
1 receptors, other than the 5-HT
1A subtype (e.g. striatum, substantia nigra and the ventricles). The PmP was not selective, inhibiting the binding of [
3H]5-HT with similar affinity (about 4–10 μM) in all the regions of the brain examined. Neither buspirone nor PmP, up to 100 μM, were active on benzodiazepine receptors.
The autoradiographic technique was therefore used to evaluate the effects of acute (10 mg/kg, p.o., 1 hr before killing) and chronic (10 mg/kg, i.p., twice a day for 21 days, 24 hr washout) treatment with buspirone in male rats. Acute treatment reduced the binding of [
3H]5-HT in all the regions of the brain studied, including those with low levels of 5-HT
1A receptors, indicating the occupancy of 5-HT
1 receptors by either buspirone or its metabolite. The binding of [
3H]flunitrazepam was decreased (16%) only in the substantia nigra. The benzodiazepine/GABA receptors present in the substantia nigra, also undergo adaptive changes after chronic treatment with buspirone: only in this region was binding to benzodiazepine receptors increased by 41% (mainly due to type I receptors) and GABA partly lost its enhancing efficacy.
Moreover, chronic administration of buspirone significantly reduced (21%) the binding of [
3H]5-HT to 5-HT
1A receptors in the dorsal raphe, whereas a significant increase in binding of [
3H]5-HT (32%) was found in the substantia nigra, which was unrelated to any modification of 5-HT
1A receptors. No significant changes were evident in the other regions of the brain.</description><subject>Animals</subject><subject>anxiolytic drugs</subject><subject>Autoradiography</subject><subject>benzodiazepine receptors</subject><subject>Biological and medical sciences</subject><subject>Brain - metabolism</subject><subject>buspirone</subject><subject>Buspirone - administration & dosage</subject><subject>Buspirone - pharmacology</subject><subject>Flunitrazepam - metabolism</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Neuropharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Psycholeptics: tranquillizer, neuroleptic</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopharmacology</subject><subject>Radioligand Assay</subject><subject>Rats</subject><subject>Receptors, GABA-A - drug effects</subject><subject>Receptors, GABA-A - metabolism</subject><subject>Receptors, Serotonin - metabolism</subject><subject>Serotonin Antagonists</subject><subject>serotonin receptors</subject><subject>Time Factors</subject><issn>0028-3908</issn><issn>1873-7064</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkcGOFCEURYnRjO3oH2jCRqOLUmgoCmZhMpmMrckkbnRNgHrYmG4ogTLp-Q__V2q64-zUFSH33Pte3kXoOSVvKaHiHSFr2TFF5GtF3yhC-r7bPEArKgfWDUTwh2j1B3mMnpTynRDCJZVn6IwKrjiVK_Tr2ntwFSePjZsrYBNH7LY5xeCwGfchhlKzqSHFhbFzmUITAbd_gZxqA-OdyUK8TWMwtzCFpmdwMNWUcZltPUxQcOPqtgmmYptNiBf4sjnnxpgxpG_ZTNs2s9R5PDxFj7zZFXh2es_R1w_XX64-djefN5-uLm86x7mqnbEw9NYxNlghR7nuiR2k7Hsq_CAJE04SbiyTjHGmlB-E8lY437cTearMmp2jV8fcKacfM5Sq96E42O1MhDQXLYmQkvLhnyDtVZss_wsUjBHWQH4EXU6lZPB6ymFv8kFTopd-9VKeXsrTiuq7fvWm2V6c8me7h_HedCy06S9PuinO7Hw20YVyj6mh5ciFe3_koJ33Z4CsiwsQHYyhNVf1mMLfF_kNZwrDiQ</recordid><startdate>19910401</startdate><enddate>19910401</enddate><creator>Gobbi, M.</creator><creator>Cavanus, S.</creator><creator>Miari, A.</creator><creator>Mennini, T.</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>7TK</scope><scope>7X8</scope></search><sort><creationdate>19910401</creationdate><title>Effect of acute and chronic administration of buspirone on serotonin and benzodiazepine receptor subtypes in the rat brain: An autoradiographic study</title><author>Gobbi, M. ; Cavanus, S. ; Miari, A. ; Mennini, T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c449t-abe75bc337b68d8250b7885516f78036c804ab38334399f769fb6cf5187f19a23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Animals</topic><topic>anxiolytic drugs</topic><topic>Autoradiography</topic><topic>benzodiazepine receptors</topic><topic>Biological and medical sciences</topic><topic>Brain - metabolism</topic><topic>buspirone</topic><topic>Buspirone - administration & dosage</topic><topic>Buspirone - pharmacology</topic><topic>Flunitrazepam - metabolism</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neuropharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Psycholeptics: tranquillizer, neuroleptic</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopharmacology</topic><topic>Radioligand Assay</topic><topic>Rats</topic><topic>Receptors, GABA-A - drug effects</topic><topic>Receptors, GABA-A - metabolism</topic><topic>Receptors, Serotonin - metabolism</topic><topic>Serotonin Antagonists</topic><topic>serotonin receptors</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gobbi, M.</creatorcontrib><creatorcontrib>Cavanus, S.</creatorcontrib><creatorcontrib>Miari, A.</creatorcontrib><creatorcontrib>Mennini, T.</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>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Neuropharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gobbi, M.</au><au>Cavanus, S.</au><au>Miari, A.</au><au>Mennini, T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of acute and chronic administration of buspirone on serotonin and benzodiazepine receptor subtypes in the rat brain: An autoradiographic study</atitle><jtitle>Neuropharmacology</jtitle><addtitle>Neuropharmacology</addtitle><date>1991-04-01</date><risdate>1991</risdate><volume>30</volume><issue>4</issue><spage>313</spage><epage>321</epage><pages>313-321</pages><issn>0028-3908</issn><eissn>1873-7064</eissn><coden>NEPHBW</coden><abstract>The affinity of buspirone and its main metabolite 1-(2-pyrimidinyl)piperazine (PmP) for serotonin
1 (5-HT
1) and benzodiazepine receptors was first evaluated by computerized receptor autoradiography. The results confirmed that buspirone is a selective 5-HT
1A ligand, since it inhibited the binding of [
3H]5-HT with lower IC
50 values (about 100 nM) in regions of the brain of the rat where this receptor subtype is predominant (such as hippocampal areas). Larger IC
50 values than 3 μM were found in areas of the brain richer in 5-HT
1 receptors, other than the 5-HT
1A subtype (e.g. striatum, substantia nigra and the ventricles). The PmP was not selective, inhibiting the binding of [
3H]5-HT with similar affinity (about 4–10 μM) in all the regions of the brain examined. Neither buspirone nor PmP, up to 100 μM, were active on benzodiazepine receptors.
The autoradiographic technique was therefore used to evaluate the effects of acute (10 mg/kg, p.o., 1 hr before killing) and chronic (10 mg/kg, i.p., twice a day for 21 days, 24 hr washout) treatment with buspirone in male rats. Acute treatment reduced the binding of [
3H]5-HT in all the regions of the brain studied, including those with low levels of 5-HT
1A receptors, indicating the occupancy of 5-HT
1 receptors by either buspirone or its metabolite. The binding of [
3H]flunitrazepam was decreased (16%) only in the substantia nigra. The benzodiazepine/GABA receptors present in the substantia nigra, also undergo adaptive changes after chronic treatment with buspirone: only in this region was binding to benzodiazepine receptors increased by 41% (mainly due to type I receptors) and GABA partly lost its enhancing efficacy.
Moreover, chronic administration of buspirone significantly reduced (21%) the binding of [
3H]5-HT to 5-HT
1A receptors in the dorsal raphe, whereas a significant increase in binding of [
3H]5-HT (32%) was found in the substantia nigra, which was unrelated to any modification of 5-HT
1A receptors. No significant changes were evident in the other regions of the brain.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>1649418</pmid><doi>10.1016/0028-3908(91)90055-G</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-3908 |
| ispartof | Neuropharmacology, 1991-04, Vol.30 (4), p.313-321 |
| issn | 0028-3908 1873-7064 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_80688147 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Animals anxiolytic drugs Autoradiography benzodiazepine receptors Biological and medical sciences Brain - metabolism buspirone Buspirone - administration & dosage Buspirone - pharmacology Flunitrazepam - metabolism In Vitro Techniques Male Medical sciences Neuropharmacology Pharmacology. Drug treatments Psycholeptics: tranquillizer, neuroleptic Psychology. Psychoanalysis. Psychiatry Psychopharmacology Radioligand Assay Rats Receptors, GABA-A - drug effects Receptors, GABA-A - metabolism Receptors, Serotonin - metabolism Serotonin Antagonists serotonin receptors Time Factors |
| title | Effect of acute and chronic administration of buspirone on serotonin and benzodiazepine receptor subtypes in the rat brain: An autoradiographic study |
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