A model of l-DOPA-induced dyskinesia in 6-hydroxydopamine lesioned mice: relation to motor and cellular parameters of nigrostriatal function

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

“…Knowledge of the plastic changes that prime the basal ganglia for a dyskinetic motor response to L-DOPA would be greatly advanced by the availability of a dyskinesia model in mice, which lend themselves to genetic manipulation of specific molecular and synaptic components. 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).…”

“…Eighty-three male mice (C57Bl/6) received unilateral 6-OHDA lesions in the right striatum using a procedure that has previously been found to produce > 75% reduction of DA fiber density (Lundblad et al 2004). The surgical procedure was the same described in Lundblad et al (2004) with one modification: instead of a burr hole, an incision was performed in the skull using the tip of an injection needle (∅ 1.25 mm).…”

“…The surgical procedure was the same described in Lundblad et al (2004) with one modification: instead of a burr hole, an incision was performed in the skull using the tip of an injection needle (∅ 1.25 mm). The mice were anaesthetized with Hypnorm®-Dormicum® (Apoteksbolaget, Sweden) (1:1:2 water mixture; 2.7 ml/kg body weight) and mounted in a stereotactic frame (Kopf Instruments; USA) with a mouse-adaptor, on a flat-skull position.…”

“…On this test, 64 mice were found to use the paw contralateral to the lesion in < 40% of all supporting wall contacts. This percentage of contralateral limb use corresponded to the mean minus two standard deviations of the values obtained in intact mice (Lundblad et al, 2004), and was therefore regarded as a cut-off value for significant motor impairment. The ultimate assessment of lesion severity was however carried out after completion of the behavioural studies by determining the striatal levels of tyrosine hydroxylase (TH) using Western immunoblotting .…”

“…Abnormal involuntary movements (AIMs) were scored using the rodent dyskinesia rating system described in Lundblad et al (2004). Briefly, the animals were placed in separate cages and scored individually every 20 minutes (1-minute monitoring periods) after injection of the tested drugs.…”