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Overexpression of plasminogen activators in the nucleus accumbens enhances cocaine-, amphetamine- and morphine-induced reward and behavioral sensitization

  • Bahi, Amine Institute of Biochemistry, University of Fribourg, Switzerland
  • Dreyer, Jean-Luc Institute of Biochemistry, University of Fribourg, Switzerland
    11.07.2007
Published in:
  • Genes, Brain and Behavior. - 2008, vol. 7, no. 2, p. 244 - 256
Activator
Addiction
Cocaine
Drugs of abuse
In vivo gene transfer
Lentivirus
Plasminogen
Plasticity
RNA interference
Serine proteases
siRNA
English 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.
Faculty
Faculté des sciences et de médecine
Department
Département de Médecine
Language
  • English
Classification
Biological sciences
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/300930
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