| Overexpression of plasminogen activators in the nucleus accumbens enhances cocaine-, amphetamine- and morphine-induced reward and behavioral sensitization. | |
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MedLine Citation:
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PMID: 17680802 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) are extracellular proteases that play a role in synaptic plasticity and remodeling. Psychostimulants induce both tPA and uPA in acute and chronic drug delivery, but cocaine induces preferentially uPA, whereas morphine and amphetamine induce preferentially tPA. Specific doxycline-regulatable lentiviruses expressing these extracellular proteases have been prepared and stereotaxically injected into the nucleus accumbens. We show that tPA-overexpressing animals show greater locomotor activity and behavioral sensitization upon morphine and amphetamine treatments. These effects could be fully suppressed by doxycycline or when tPA had been silenced using small interfering RNAs (siRNAs)-expressing lentiviruses. Furthermore, animals infected with lentiviruses expressing uPA show enhanced conditional place preference for cocaine compared with tPA-overexpressing animals. In contrast, tPA-overexpressing animals when administered amphetamine or morphine showed greater place preference compared with uPA-overexpressing animals. The effects are suppressed when tPA has been silenced using specific siRNAs-expressing vectors. Tissue-type plasminogen activator and uPA possibly induce distinct behaviors, which may be interpreted according to their differential pattern of activation and downstream targets. Taken together, these data add further evidence for a significant function of extracellular proteases tPA and uPA in addiction and suggest a differential role of plasminogen activators in this context. |
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Authors:
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A Bahi; J-L Dreyer |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-08-03 |
Journal Detail:
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Title: Genes, brain, and behavior Volume: 7 ISSN: 1601-183X ISO Abbreviation: Genes Brain Behav. Publication Date: 2008 Mar |
Date Detail:
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Created Date: 2008-03-05 Completed Date: 2008-05-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101129617 Medline TA: Genes Brain Behav Country: England |
Other Details:
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Languages: eng Pagination: 244-56 Citation Subset: IM |
Affiliation:
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Institute of Biochemistry, University of Fribourg, Fribourg, Switzerland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amphetamine
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pharmacology* Animals Base Sequence Behavior, Animal / drug effects, physiology* Cocaine / pharmacology* DNA Primers Doxycycline / pharmacology* Lentivirus / drug effects, genetics Male Molecular Sequence Data Morphine / pharmacology* Nucleus Accumbens / drug effects, physiology* Plasminogen Activators / genetics* Polymerase Chain Reaction RNA, Small Interfering / genetics RNA, Viral / genetics Rats Rats, Wistar Reward* Tissue Plasminogen Activator / genetics* Viral Proteins / genetics |
| Chemical | |
Reg. No./Substance:
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0/DNA Primers; 0/RNA, Small Interfering; 0/RNA, Viral; 0/Viral Proteins; 300-62-9/Amphetamine; 50-36-2/Cocaine; 564-25-0/Doxycycline; 57-27-2/Morphine; EC 3.4.21.-/Plasminogen Activators; EC 3.4.21.68/Tissue Plasminogen Activator |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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