Decreased Caffeine-Induced Locomotor Activity via Microinjection of CART Peptide into the Nucleus Accumbens Is Linked to Inhibition of the pCaMKIIa-D3R Interaction
The purpose of this study was to characterize the inhibitory modulation of cocaine- and amphetamine-regulated transcript (CART) peptides, particularly with respect to the function of the D3 dopamine receptor (D3R), which is activated by its interaction with phosphorylated CaMKIIα (pCaMKIIα) in the n...
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| Veröffentlicht in: | PloS one 2016-07, Vol.11 (7), p.e0159104-e0159104 |
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| creator | Fu, Qiang Zhou, Xiaoyan Dong, Yun Huang, Yonghong Yang, Jianhua Oh, Ki-Wan Hu, Zhenzhen |
| description | The purpose of this study was to characterize the inhibitory modulation of cocaine- and amphetamine-regulated transcript (CART) peptides, particularly with respect to the function of the D3 dopamine receptor (D3R), which is activated by its interaction with phosphorylated CaMKIIα (pCaMKIIα) in the nucleus accumbens (NAc). After repeated oral administration of caffeine (30 mg/kg) for five days, microinjection of CART peptide (0.08 μM/0.5 μl/hemisphere) into the NAc affected locomotor behavior. The pCaMKIIα-D3R interaction, D3R phosphorylation and cAMP/PKA/phosphorylated CREB (pCREB) signaling pathway activity were measured in NAc tissues, and Ca2+ influx and pCaMKIIα levels were measured in cultured NAc neurons. We found that CART attenuated the caffeine-mediated enhancement of depolarization-induced Ca2+ influx and CaMKIIα phosphorylation in cultured NAc neurons. Repeated microinjection of CART peptides into the NAc decreased the caffeine-induced enhancement of Ca2+ channels activity, pCaMKIIα levels, the pCaMKIIα-D3R interaction, D3R phosphorylation, cAMP levels, PKA activity and pCREB levels in the NAc. Furthermore, behavioral sensitization was observed in rats that received five-day administration of caffeine following microinjection of saline but not in rats that were treated with caffeine following microinjection of CART peptide. These results suggest that caffeine-induced CREB phosphorylation in the NAc was ameliorated by CART peptide due to its inhibition of D3R phosphorylation. These effects of CART peptides may play a compensatory role by inhibiting locomotor behavior in rats. |
| doi_str_mv | 10.1371/journal.pone.0159104 |
| format | Article |
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After repeated oral administration of caffeine (30 mg/kg) for five days, microinjection of CART peptide (0.08 μM/0.5 μl/hemisphere) into the NAc affected locomotor behavior. The pCaMKIIα-D3R interaction, D3R phosphorylation and cAMP/PKA/phosphorylated CREB (pCREB) signaling pathway activity were measured in NAc tissues, and Ca2+ influx and pCaMKIIα levels were measured in cultured NAc neurons. We found that CART attenuated the caffeine-mediated enhancement of depolarization-induced Ca2+ influx and CaMKIIα phosphorylation in cultured NAc neurons. Repeated microinjection of CART peptides into the NAc decreased the caffeine-induced enhancement of Ca2+ channels activity, pCaMKIIα levels, the pCaMKIIα-D3R interaction, D3R phosphorylation, cAMP levels, PKA activity and pCREB levels in the NAc. Furthermore, behavioral sensitization was observed in rats that received five-day administration of caffeine following microinjection of saline but not in rats that were treated with caffeine following microinjection of CART peptide. These results suggest that caffeine-induced CREB phosphorylation in the NAc was ameliorated by CART peptide due to its inhibition of D3R phosphorylation. These effects of CART peptides may play a compensatory role by inhibiting locomotor behavior in rats.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0159104</identifier><identifier>PMID: 27404570</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Amphetamines ; Animal behavior ; Animal tissues ; Animals ; Biology and Life Sciences ; Caffeine ; Caffeine - antagonists & inhibitors ; Caffeine - pharmacology ; Calcium - metabolism ; Calcium channels ; Calcium influx ; Calcium ions ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism ; Cocaine ; Cocaine- and amphetamine-regulated transcript protein ; Cyclic AMP - metabolism ; Cyclic AMP response element-binding protein ; Cyclic AMP Response Element-Binding Protein - metabolism ; Cyclic AMP-Dependent Protein Kinases - metabolism ; Depolarization ; Dopamine ; Dopamine D3 receptors ; Gene Expression Regulation, Enzymologic - drug effects ; Inhibition ; Kinases ; Locomotion - drug effects ; Locomotor activity ; Male ; Medicine and Health Sciences ; Microinjection ; Microinjections ; Nerve Tissue Proteins - administration & dosage ; Nerve Tissue Proteins - pharmacology ; Neurons ; Neurons - cytology ; Neurons - drug effects ; Neurons - metabolism ; Nuclei ; Nucleus accumbens ; Nucleus Accumbens - cytology ; Nucleus Accumbens - drug effects ; Nucleus Accumbens - metabolism ; Oral administration ; Peptides ; Phosphoproteins - metabolism ; Phosphorylation ; Physical Sciences ; Protein Binding - drug effects ; Protein kinase A ; Rats ; Rats, Sprague-Dawley ; Receptors, Dopamine D3 - metabolism ; Research and Analysis Methods ; Rodents ; Signal transduction ; Signal Transduction - drug effects ; Signaling ; Transcription</subject><ispartof>PloS one, 2016-07, Vol.11 (7), p.e0159104-e0159104</ispartof><rights>2016 Fu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Fu et al 2016 Fu et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c559t-b5f94108fd618e1f4a202a228b22dfed8c79c8960ef9b685c1d31ba0caac76203</citedby><cites>FETCH-LOGICAL-c559t-b5f94108fd618e1f4a202a228b22dfed8c79c8960ef9b685c1d31ba0caac76203</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4942143/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4942143/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27404570$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fu, Qiang</creatorcontrib><creatorcontrib>Zhou, Xiaoyan</creatorcontrib><creatorcontrib>Dong, Yun</creatorcontrib><creatorcontrib>Huang, Yonghong</creatorcontrib><creatorcontrib>Yang, Jianhua</creatorcontrib><creatorcontrib>Oh, Ki-Wan</creatorcontrib><creatorcontrib>Hu, Zhenzhen</creatorcontrib><title>Decreased Caffeine-Induced Locomotor Activity via Microinjection of CART Peptide into the Nucleus Accumbens Is Linked to Inhibition of the pCaMKIIa-D3R Interaction</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The purpose of this study was to characterize the inhibitory modulation of cocaine- and amphetamine-regulated transcript (CART) peptides, particularly with respect to the function of the D3 dopamine receptor (D3R), which is activated by its interaction with phosphorylated CaMKIIα (pCaMKIIα) in the nucleus accumbens (NAc). After repeated oral administration of caffeine (30 mg/kg) for five days, microinjection of CART peptide (0.08 μM/0.5 μl/hemisphere) into the NAc affected locomotor behavior. The pCaMKIIα-D3R interaction, D3R phosphorylation and cAMP/PKA/phosphorylated CREB (pCREB) signaling pathway activity were measured in NAc tissues, and Ca2+ influx and pCaMKIIα levels were measured in cultured NAc neurons. We found that CART attenuated the caffeine-mediated enhancement of depolarization-induced Ca2+ influx and CaMKIIα phosphorylation in cultured NAc neurons. Repeated microinjection of CART peptides into the NAc decreased the caffeine-induced enhancement of Ca2+ channels activity, pCaMKIIα levels, the pCaMKIIα-D3R interaction, D3R phosphorylation, cAMP levels, PKA activity and pCREB levels in the NAc. Furthermore, behavioral sensitization was observed in rats that received five-day administration of caffeine following microinjection of saline but not in rats that were treated with caffeine following microinjection of CART peptide. These results suggest that caffeine-induced CREB phosphorylation in the NAc was ameliorated by CART peptide due to its inhibition of D3R phosphorylation. These effects of CART peptides may play a compensatory role by inhibiting locomotor behavior in rats.</description><subject>Amphetamines</subject><subject>Animal behavior</subject><subject>Animal tissues</subject><subject>Animals</subject><subject>Biology and Life Sciences</subject><subject>Caffeine</subject><subject>Caffeine - antagonists & inhibitors</subject><subject>Caffeine - pharmacology</subject><subject>Calcium - metabolism</subject><subject>Calcium channels</subject><subject>Calcium influx</subject><subject>Calcium ions</subject><subject>Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism</subject><subject>Cocaine</subject><subject>Cocaine- and amphetamine-regulated transcript protein</subject><subject>Cyclic AMP - metabolism</subject><subject>Cyclic AMP response element-binding protein</subject><subject>Cyclic AMP Response Element-Binding Protein - metabolism</subject><subject>Cyclic AMP-Dependent Protein Kinases - metabolism</subject><subject>Depolarization</subject><subject>Dopamine</subject><subject>Dopamine D3 receptors</subject><subject>Gene Expression Regulation, Enzymologic - drug effects</subject><subject>Inhibition</subject><subject>Kinases</subject><subject>Locomotion - drug effects</subject><subject>Locomotor activity</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Microinjection</subject><subject>Microinjections</subject><subject>Nerve Tissue Proteins - administration & dosage</subject><subject>Nerve Tissue Proteins - pharmacology</subject><subject>Neurons</subject><subject>Neurons - cytology</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Nuclei</subject><subject>Nucleus accumbens</subject><subject>Nucleus Accumbens - cytology</subject><subject>Nucleus Accumbens - drug effects</subject><subject>Nucleus Accumbens - metabolism</subject><subject>Oral administration</subject><subject>Peptides</subject><subject>Phosphoproteins - metabolism</subject><subject>Phosphorylation</subject><subject>Physical Sciences</subject><subject>Protein Binding - drug effects</subject><subject>Protein kinase A</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Dopamine D3 - 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antagonists & inhibitors</topic><topic>Caffeine - pharmacology</topic><topic>Calcium - metabolism</topic><topic>Calcium channels</topic><topic>Calcium influx</topic><topic>Calcium ions</topic><topic>Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism</topic><topic>Cocaine</topic><topic>Cocaine- and amphetamine-regulated transcript protein</topic><topic>Cyclic AMP - metabolism</topic><topic>Cyclic AMP response element-binding protein</topic><topic>Cyclic AMP Response Element-Binding Protein - metabolism</topic><topic>Cyclic AMP-Dependent Protein Kinases - metabolism</topic><topic>Depolarization</topic><topic>Dopamine</topic><topic>Dopamine D3 receptors</topic><topic>Gene Expression Regulation, Enzymologic - drug effects</topic><topic>Inhibition</topic><topic>Kinases</topic><topic>Locomotion - drug effects</topic><topic>Locomotor activity</topic><topic>Male</topic><topic>Medicine and Health Sciences</topic><topic>Microinjection</topic><topic>Microinjections</topic><topic>Nerve Tissue Proteins - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fu, Qiang</au><au>Zhou, Xiaoyan</au><au>Dong, Yun</au><au>Huang, Yonghong</au><au>Yang, Jianhua</au><au>Oh, Ki-Wan</au><au>Hu, Zhenzhen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Decreased Caffeine-Induced Locomotor Activity via Microinjection of CART Peptide into the Nucleus Accumbens Is Linked to Inhibition of the pCaMKIIa-D3R Interaction</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-07-01</date><risdate>2016</risdate><volume>11</volume><issue>7</issue><spage>e0159104</spage><epage>e0159104</epage><pages>e0159104-e0159104</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The purpose of this study was to characterize the inhibitory modulation of cocaine- and amphetamine-regulated transcript (CART) peptides, particularly with respect to the function of the D3 dopamine receptor (D3R), which is activated by its interaction with phosphorylated CaMKIIα (pCaMKIIα) in the nucleus accumbens (NAc). After repeated oral administration of caffeine (30 mg/kg) for five days, microinjection of CART peptide (0.08 μM/0.5 μl/hemisphere) into the NAc affected locomotor behavior. The pCaMKIIα-D3R interaction, D3R phosphorylation and cAMP/PKA/phosphorylated CREB (pCREB) signaling pathway activity were measured in NAc tissues, and Ca2+ influx and pCaMKIIα levels were measured in cultured NAc neurons. We found that CART attenuated the caffeine-mediated enhancement of depolarization-induced Ca2+ influx and CaMKIIα phosphorylation in cultured NAc neurons. Repeated microinjection of CART peptides into the NAc decreased the caffeine-induced enhancement of Ca2+ channels activity, pCaMKIIα levels, the pCaMKIIα-D3R interaction, D3R phosphorylation, cAMP levels, PKA activity and pCREB levels in the NAc. Furthermore, behavioral sensitization was observed in rats that received five-day administration of caffeine following microinjection of saline but not in rats that were treated with caffeine following microinjection of CART peptide. These results suggest that caffeine-induced CREB phosphorylation in the NAc was ameliorated by CART peptide due to its inhibition of D3R phosphorylation. These effects of CART peptides may play a compensatory role by inhibiting locomotor behavior in rats.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27404570</pmid><doi>10.1371/journal.pone.0159104</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1817094602 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Amphetamines Animal behavior Animal tissues Animals Biology and Life Sciences Caffeine Caffeine - antagonists & inhibitors Caffeine - pharmacology Calcium - metabolism Calcium channels Calcium influx Calcium ions Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism Cocaine Cocaine- and amphetamine-regulated transcript protein Cyclic AMP - metabolism Cyclic AMP response element-binding protein Cyclic AMP Response Element-Binding Protein - metabolism Cyclic AMP-Dependent Protein Kinases - metabolism Depolarization Dopamine Dopamine D3 receptors Gene Expression Regulation, Enzymologic - drug effects Inhibition Kinases Locomotion - drug effects Locomotor activity Male Medicine and Health Sciences Microinjection Microinjections Nerve Tissue Proteins - administration & dosage Nerve Tissue Proteins - pharmacology Neurons Neurons - cytology Neurons - drug effects Neurons - metabolism Nuclei Nucleus accumbens Nucleus Accumbens - cytology Nucleus Accumbens - drug effects Nucleus Accumbens - metabolism Oral administration Peptides Phosphoproteins - metabolism Phosphorylation Physical Sciences Protein Binding - drug effects Protein kinase A Rats Rats, Sprague-Dawley Receptors, Dopamine D3 - metabolism Research and Analysis Methods Rodents Signal transduction Signal Transduction - drug effects Signaling Transcription |
| title | Decreased Caffeine-Induced Locomotor Activity via Microinjection of CART Peptide into the Nucleus Accumbens Is Linked to Inhibition of the pCaMKIIa-D3R Interaction |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T07%3A51%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Decreased%20Caffeine-Induced%20Locomotor%20Activity%20via%20Microinjection%20of%20CART%20Peptide%20into%20the%20Nucleus%20Accumbens%20Is%20Linked%20to%20Inhibition%20of%20the%20pCaMKIIa-D3R%20Interaction&rft.jtitle=PloS%20one&rft.au=Fu,%20Qiang&rft.date=2016-07-01&rft.volume=11&rft.issue=7&rft.spage=e0159104&rft.epage=e0159104&rft.pages=e0159104-e0159104&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0159104&rft_dat=%3Cproquest_plos_%3E1804197232%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1817094602&rft_id=info:pmid/27404570&rft_doaj_id=oai_doaj_org_article_772374478b45420c9a8a9480ea7b2b3a&rfr_iscdi=true |