Bahi, Amine Boyer, Frederic Kafri, Tal Dreyer, Jean-Luc 2006-07-20 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. application/pdf https://folia.unifr.ch/global/documents/300249 https://folia.unifr.ch/documents/300249/files/dreier_suv.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1471-4159.2006.04013.x info:eu-repo/semantics/openAccess License undefined Journal of Neurochemistry. - 2006, vol. 98, no. 5, p. 1619–1631 addiction in vivo gene transfer lentivirus plasticity small interfering RNA urokinase-type plasminogen activator info:eu-repo/classification/udc/57 Silencing urokinase in the ventral tegmental area in vivo induces changes in cocaine-induced hyperlocomotion http://purl.org/coar/resource_type/c_6501