Postnatal alterations in GABAB receptor tone produce sensorimotor gating deficits and protein level differences in adulthood
•GABAB agonist or antagonist on PND 7, 9, and 12 produced PPI deficits in adulthood.•Proteins associated with GABA signaling and plasticity were altered in adulthood.•Differences in the effects of the GABAB ligands were observed between genders. The GABA transmitter system plays a vital role in modu...
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| Veröffentlicht in: | International journal of developmental neuroscience 2015-04, Vol.41 (1), p.17-27 |
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| container_title | International journal of developmental neuroscience |
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| creator | Bolton, Monica M. Heaney, Chelcie F. Murtishaw, Andrew S. Sabbagh, Jonathan J. Magcalas, Christy M. Kinney, Jefferson W. |
| description | •GABAB agonist or antagonist on PND 7, 9, and 12 produced PPI deficits in adulthood.•Proteins associated with GABA signaling and plasticity were altered in adulthood.•Differences in the effects of the GABAB ligands were observed between genders.
The GABA transmitter system plays a vital role in modulating synaptic formation and activity during development. The GABAB receptor subtype in particular has been implicated in cell migration, promotion of neuronal differentiation, neurite outgrowth, and synapse formation but it's role in development is not well characterized. In order to investigate the effects of brief alterations in GABAB signaling in development, we administered to rats the GABAB agonist baclofen (2.0mg/kg) or antagonist phaclofen (0.3mg/kg) on postnatal days 7, 9, and 12, and evaluated sensorimotor gating in adulthood. We also examined tissue for changes in multiple proteins associated with GABAB receptor function and proteins associated with synapse formation. Our data indicate that early postnatal alterations to GABAB receptor-mediated signaling produced sex differences in sensorimotor gating in adulthood. Additionally, we found differences in GABAB receptor subunits and kalirin protein levels in the brain versus saline treated controls. Our data demonstrate that a subtle alteration in GABAB receptor function in early postnatal life induces changes that persist into adulthood. |
| doi_str_mv | 10.1016/j.ijdevneu.2014.10.001 |
| format | Article |
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The GABA transmitter system plays a vital role in modulating synaptic formation and activity during development. The GABAB receptor subtype in particular has been implicated in cell migration, promotion of neuronal differentiation, neurite outgrowth, and synapse formation but it's role in development is not well characterized. In order to investigate the effects of brief alterations in GABAB signaling in development, we administered to rats the GABAB agonist baclofen (2.0mg/kg) or antagonist phaclofen (0.3mg/kg) on postnatal days 7, 9, and 12, and evaluated sensorimotor gating in adulthood. We also examined tissue for changes in multiple proteins associated with GABAB receptor function and proteins associated with synapse formation. Our data indicate that early postnatal alterations to GABAB receptor-mediated signaling produced sex differences in sensorimotor gating in adulthood. Additionally, we found differences in GABAB receptor subunits and kalirin protein levels in the brain versus saline treated controls. Our data demonstrate that a subtle alteration in GABAB receptor function in early postnatal life induces changes that persist into adulthood.</description><identifier>ISSN: 0736-5748</identifier><identifier>EISSN: 1873-474X</identifier><identifier>DOI: 10.1016/j.ijdevneu.2014.10.001</identifier><identifier>PMID: 25314921</identifier><language>eng</language><publisher>United States: Elsevier Ltd</publisher><subject>Acoustic Stimulation ; Age Factors ; Animals ; Animals, Newborn ; Baclofen - analogs & derivatives ; Baclofen - toxicity ; Behavior ; Body Weight - drug effects ; Brain - metabolism ; Development ; Disease Models, Animal ; Female ; GABA Antagonists - toxicity ; GABA-B Receptor Agonists - toxicity ; GABAB receptor ; Gait Disorders, Neurologic - chemically induced ; Gait Disorders, Neurologic - metabolism ; Gait Disorders, Neurologic - pathology ; Gene Expression Regulation, Developmental - drug effects ; Gene Expression Regulation, Developmental - physiology ; Male ; Pregnancy ; Prepulse inhibition ; Prepulse Inhibition - drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA-B - metabolism ; Sensory Gating - drug effects ; Signal Transduction - drug effects ; Signal Transduction - physiology</subject><ispartof>International journal of developmental neuroscience, 2015-04, Vol.41 (1), p.17-27</ispartof><rights>2014 ISDN</rights><rights>2015 ISDN</rights><rights>Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1016%2Fj.ijdevneu.2014.10.001$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1016%2Fj.ijdevneu.2014.10.001$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25314921$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bolton, Monica M.</creatorcontrib><creatorcontrib>Heaney, Chelcie F.</creatorcontrib><creatorcontrib>Murtishaw, Andrew S.</creatorcontrib><creatorcontrib>Sabbagh, Jonathan J.</creatorcontrib><creatorcontrib>Magcalas, Christy M.</creatorcontrib><creatorcontrib>Kinney, Jefferson W.</creatorcontrib><title>Postnatal alterations in GABAB receptor tone produce sensorimotor gating deficits and protein level differences in adulthood</title><title>International journal of developmental neuroscience</title><addtitle>Int J Dev Neurosci</addtitle><description>•GABAB agonist or antagonist on PND 7, 9, and 12 produced PPI deficits in adulthood.•Proteins associated with GABA signaling and plasticity were altered in adulthood.•Differences in the effects of the GABAB ligands were observed between genders.
The GABA transmitter system plays a vital role in modulating synaptic formation and activity during development. The GABAB receptor subtype in particular has been implicated in cell migration, promotion of neuronal differentiation, neurite outgrowth, and synapse formation but it's role in development is not well characterized. In order to investigate the effects of brief alterations in GABAB signaling in development, we administered to rats the GABAB agonist baclofen (2.0mg/kg) or antagonist phaclofen (0.3mg/kg) on postnatal days 7, 9, and 12, and evaluated sensorimotor gating in adulthood. We also examined tissue for changes in multiple proteins associated with GABAB receptor function and proteins associated with synapse formation. Our data indicate that early postnatal alterations to GABAB receptor-mediated signaling produced sex differences in sensorimotor gating in adulthood. Additionally, we found differences in GABAB receptor subunits and kalirin protein levels in the brain versus saline treated controls. Our data demonstrate that a subtle alteration in GABAB receptor function in early postnatal life induces changes that persist into adulthood.</description><subject>Acoustic Stimulation</subject><subject>Age Factors</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Baclofen - analogs & derivatives</subject><subject>Baclofen - toxicity</subject><subject>Behavior</subject><subject>Body Weight - drug effects</subject><subject>Brain - metabolism</subject><subject>Development</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>GABA Antagonists - toxicity</subject><subject>GABA-B Receptor Agonists - toxicity</subject><subject>GABAB receptor</subject><subject>Gait Disorders, Neurologic - chemically induced</subject><subject>Gait Disorders, Neurologic - metabolism</subject><subject>Gait Disorders, Neurologic - pathology</subject><subject>Gene Expression Regulation, Developmental - drug effects</subject><subject>Gene Expression Regulation, Developmental - physiology</subject><subject>Male</subject><subject>Pregnancy</subject><subject>Prepulse inhibition</subject><subject>Prepulse Inhibition - drug effects</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, GABA-B - metabolism</subject><subject>Sensory Gating - drug effects</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - physiology</subject><issn>0736-5748</issn><issn>1873-474X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFPGzEQha2KqgTav4B87GWDveu1vbcGCJAIAYdS9WY561nqyLHD2huExI_H20CvPVl68-aT5z2ETiiZUkL56Xpq1wZ2HoZpSSjL4pQQ-glNqBRVwQT7fYAmRFS8qAWTh-goxjUhpK4J-4IOy7qirCnpBL3eh5i8Ttph7RL0OtngI7YeX83OZme4hxa2KfQ4BQ942wcztIAj-Bh6uwnj5DHv-EdsoLOtTRFrb0ZjggxxsAOHje066MG38JeszeDSnxDMV_S50y7Ct_f3GD1czn-eXxc3d1eL89lNASVraMEpF7wRK90I0TEQhAohmKnaUkNJSQeik4xxLmUHUqwqyRpW1u2KG22Ihqo6Rt_33PytpwFiUhsbW3BOewhDVJRz2jSylCRbT96tw2oDRm3zlbp_UR-JZcNib3i2Dl7-zSlRYy9qrT56UWMvo557UcuL2-VieTH_dTt_GHWauxhZP_YsyMfvLPQqtnaMydice1Im2P-Aqzcyw56S</recordid><startdate>201504</startdate><enddate>201504</enddate><creator>Bolton, Monica M.</creator><creator>Heaney, Chelcie F.</creator><creator>Murtishaw, Andrew S.</creator><creator>Sabbagh, Jonathan J.</creator><creator>Magcalas, Christy M.</creator><creator>Kinney, Jefferson W.</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>201504</creationdate><title>Postnatal alterations in GABAB receptor tone produce sensorimotor gating deficits and protein level differences in adulthood</title><author>Bolton, Monica M. ; Heaney, Chelcie F. ; Murtishaw, Andrew S. ; Sabbagh, Jonathan J. ; Magcalas, Christy M. ; Kinney, Jefferson W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-e2491-6167697ba977f4e7017774d3c2ae210fe7f8446688fe87b3849425cb6dad0ae33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Acoustic Stimulation</topic><topic>Age Factors</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Baclofen - analogs & derivatives</topic><topic>Baclofen - toxicity</topic><topic>Behavior</topic><topic>Body Weight - drug effects</topic><topic>Brain - metabolism</topic><topic>Development</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>GABA Antagonists - toxicity</topic><topic>GABA-B Receptor Agonists - toxicity</topic><topic>GABAB receptor</topic><topic>Gait Disorders, Neurologic - chemically induced</topic><topic>Gait Disorders, Neurologic - metabolism</topic><topic>Gait Disorders, Neurologic - pathology</topic><topic>Gene Expression Regulation, Developmental - drug effects</topic><topic>Gene Expression Regulation, Developmental - physiology</topic><topic>Male</topic><topic>Pregnancy</topic><topic>Prepulse inhibition</topic><topic>Prepulse Inhibition - drug effects</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, GABA-B - metabolism</topic><topic>Sensory Gating - drug effects</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bolton, Monica M.</creatorcontrib><creatorcontrib>Heaney, Chelcie F.</creatorcontrib><creatorcontrib>Murtishaw, Andrew S.</creatorcontrib><creatorcontrib>Sabbagh, Jonathan J.</creatorcontrib><creatorcontrib>Magcalas, Christy M.</creatorcontrib><creatorcontrib>Kinney, Jefferson W.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of developmental neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bolton, Monica M.</au><au>Heaney, Chelcie F.</au><au>Murtishaw, Andrew S.</au><au>Sabbagh, Jonathan J.</au><au>Magcalas, Christy M.</au><au>Kinney, Jefferson W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Postnatal alterations in GABAB receptor tone produce sensorimotor gating deficits and protein level differences in adulthood</atitle><jtitle>International journal of developmental neuroscience</jtitle><addtitle>Int J Dev Neurosci</addtitle><date>2015-04</date><risdate>2015</risdate><volume>41</volume><issue>1</issue><spage>17</spage><epage>27</epage><pages>17-27</pages><issn>0736-5748</issn><eissn>1873-474X</eissn><abstract>•GABAB agonist or antagonist on PND 7, 9, and 12 produced PPI deficits in adulthood.•Proteins associated with GABA signaling and plasticity were altered in adulthood.•Differences in the effects of the GABAB ligands were observed between genders.
The GABA transmitter system plays a vital role in modulating synaptic formation and activity during development. The GABAB receptor subtype in particular has been implicated in cell migration, promotion of neuronal differentiation, neurite outgrowth, and synapse formation but it's role in development is not well characterized. In order to investigate the effects of brief alterations in GABAB signaling in development, we administered to rats the GABAB agonist baclofen (2.0mg/kg) or antagonist phaclofen (0.3mg/kg) on postnatal days 7, 9, and 12, and evaluated sensorimotor gating in adulthood. We also examined tissue for changes in multiple proteins associated with GABAB receptor function and proteins associated with synapse formation. Our data indicate that early postnatal alterations to GABAB receptor-mediated signaling produced sex differences in sensorimotor gating in adulthood. Additionally, we found differences in GABAB receptor subunits and kalirin protein levels in the brain versus saline treated controls. Our data demonstrate that a subtle alteration in GABAB receptor function in early postnatal life induces changes that persist into adulthood.</abstract><cop>United States</cop><pub>Elsevier Ltd</pub><pmid>25314921</pmid><doi>10.1016/j.ijdevneu.2014.10.001</doi><tpages>11</tpages></addata></record> |
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| subjects | Acoustic Stimulation Age Factors Animals Animals, Newborn Baclofen - analogs & derivatives Baclofen - toxicity Behavior Body Weight - drug effects Brain - metabolism Development Disease Models, Animal Female GABA Antagonists - toxicity GABA-B Receptor Agonists - toxicity GABAB receptor Gait Disorders, Neurologic - chemically induced Gait Disorders, Neurologic - metabolism Gait Disorders, Neurologic - pathology Gene Expression Regulation, Developmental - drug effects Gene Expression Regulation, Developmental - physiology Male Pregnancy Prepulse inhibition Prepulse Inhibition - drug effects Random Allocation Rats Rats, Sprague-Dawley Receptors, GABA-B - metabolism Sensory Gating - drug effects Signal Transduction - drug effects Signal Transduction - physiology |
| title | Postnatal alterations in GABAB receptor tone produce sensorimotor gating deficits and protein level differences in adulthood |
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