Back
Full-text
Journal article

Silencing urokinase in the ventral tegmental area in vivo induces changes in cocaine-induced hyperlocomotion.

  • 2006-08-23
Published in:
  • Journal of neurochemistry. - 2006
Animals
Behavior, Animal
Blotting, Northern
Cell Line
Cocaine
Dopamine Uptake Inhibitors
Doxycycline
Gene Expression
Genetic Vectors
Green Fluorescent Proteins
Humans
Immunohistochemistry
Lentivirus
Motor Activity
Mutagenesis
RNA, Messenger
Rats
Rats, Wistar
Reverse Transcriptase Polymerase Chain Reaction
Transfection
Urokinase-Type Plasminogen Activator
Ventral Tegmental Area
English Serine proteases in the nervous system have functional roles in neural plasticity. Among them, urokinase-type plasminogen activator (uPA) exerts a variety of functions during development, and is involved in learning and memory. Furthermore, psychostimulants strongly induce uPA expression in the mesolimbic dopaminergic pathway. In this study, doxycycline-regulatable lentiviruses expressing either uPA, a dominant-negative form of uPA, or non-regulatable lentiviruses expressing small interfering RNAs (siRNAs) targeted against uPA have been prepared and injected into the ventral tegmental area (VTA) of rat brains. Over-expression of uPA in the VTA induces doxycycline-dependent expression of its receptor, uPAR, but not its inhibitor, plasminogen activator inhibitor-1 (PAI-1). uPAR expression in the VTA is repressed upon silencing of uPA with lentiviruses expressing siRNAs. In addition, over-expression of uPA in the VTA promotes a 15-fold increase in locomotion activity upon cocaine delivery. Animals expressing the dominant-negative form of uPA did not display such hyperlocomotor activity. These cocaine-induced behavioural changes, associated with uPA expression, could be suppressed in the presence of doxycycline or uPA-specific siRNAs expressing lentiviruses. These data strongly support the major role of urokinase in cocaine-mediated plasticity changes.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://sonar.ch/global/documents/93345
Statistics
Document views: 23 File downloads:
  • Full-text: 0