Striatal fosB Expression Is Causally Linked with l-DOPA-Induced Abnormal Involuntary Movements and the Associated Upregulation of Striatal Prodynorphin mRNA in a Rat Model of Parkinson's Disease

Time course of striatal ΔFosB‐like immunoreactivity and prodynorphin mRNA levels after discontinuation of chronic dopaminomimetic treatment

“…This quantitative analysis was carried out separately in the medial and the lateral part of the CPu because the rat striatum shows a functionally important medio-lateral topography , which is also reflected in various drug-specific patterns of gene induction (Moratalla et al, 1996;Andersson et al, 1999;Cenci et al, 1999;Saka et al, 1999). In the DA-denervated CPu, the levels of FosB/DFosB-like immunoreactivity showed a slow decline after discontinuation of chronic L-DOPA treatment.…”

“…Sections through the striatum (16 mm thick) were cut using a cryostat, thawmounted onto microscope slides (SuperFrost Plus; Menzel Glazer, Germany), and stored at À20 8C. Immunohistochemistry was performed using a standard peroxidase-based method (Vectastain Elite ABC Kit, Vector Laboratories Inc., Burlingame, CA, USA) as described by Andersson et al (1999). The primary antiserum was purchased from Santa Cruz Biotechnology Inc. (Santa Cruz, CA, USA) and used at a dilution of 1 : 15000.…”

“…In situ hybridization histochemistry was performed using 48-mer oligonucleotides complementary to PDyn mRNA, which had been labelled at the 3 0 end with [a-35 S]dATP, as described previously (Cenci et al, 1998;Andersson et al, 1999).…”

Pharmacological validation of a mouse model of l-DOPA-induced dyskinesia

“…In a recent study (Lundblad et al, 2004) we have shown that unilaterally 6-hydroxydopamine (6-OHDA) lesioned mice treated with L-DOPA exhibit abnormal movements similar to those described in a validated model of L-DOPA-induced dyskinesia in the rat (for review see Cenci et al, 2002b). Mice that develop abnormal movements under L-DOPA show striatal upregulation of ΔFosB-like immunoreactivity and prodynorphin mRNA, two well-established markers of maladaptive molecular plasticity in other animal models of L-DOPA-induced dyskinesia (Doucet et al, 1996;Andersson et al, 1999). These results suggest that it is possible to simulate L-DOPA-induced dyskinesia in the mouse, but do not provide any information on the predictive validity and clinical relevance of the mouse dyskinesia model.…”

“…The present results indicate that, also in the mouse, locomotive AIMs provide a less sensitive behavioural measure of dyskinesia than do axial, limb and orolingual AIMs. Anatomical mapping of FosB/∆FosB immunoreactivity has shown that axial, limb and orolingual AIMs are associated with an upregulation of this marker in the sensorimotor (lateral) part of the striatum, while locomotive AIMs are linked to increased ∆FosB expression in the medial striatum (Andersson et al, 1999;Lundblad et al, 2004). In both rats and mice, the medial striatum is involved with associative and limbic-related functions and plays a prominent role in the control of locomotor activities.…”