5 to 4 mg/kg (Von Voigtlander & Moore, 1973; Akerud et al., 2001) are much higher than those typically used in rats (0.05–0.25 mg/kg). The aim of the present study was to perform a more extensive morphological and behavioural
characterisation of the unilateral intranigral 6-OHDA selleck chemical lesion mouse model and correlate the extent of damage to the mesostriatal DA projections with the magnitude of impairment seen in a battery of tests commonly used for assessment of motor impairments in rats. Based on this information we have devised a set of behavioural criteria that can be used to indentify well lesioned mice prior to any restorative or disease modifying intervention. In addition to the standard drug-induced rotation, cylinder and stepping tests, we have explored the usefulness of a novel sensorimotor integration test, the corridor task, originally developed for studies in rats (Dowd et al., 2005a), for quantification of behavioural impairments in 6-OHDA-lesioned mice. Selumetinib in vitro A total of 129 female mice (Charles River; NMRI strain, weighing 25–35 g at the time of surgery)
were used in this study. 6-OHDA was injected unilaterally in the substantia nigra in 122 mice. The remaining seven mice served as intact controls. All mice were subjected to behavioural analysis in all tests described below and, based on the wide range of motor impairments seen in both drug-induced rotation tests and the corridor task, 40 of the 6-OHDA-lesioned mice were selected for further analysis in the present study, while the others were used in a different experiment. The selection was made so as to include animals that represented the full range of motor deficits induced by the intranigral 6-OHDA lesion, defined as mild, intermediate and severe impairments. In all behavioural tests the animals were numbered without any indication of treatment. The stability of the motor deficits over time was studied in seven
mice that exhibited severe behavioural deficits in the early post-lesion time-point. Beginning 6 weeks after lesioning, these mice were tested at regular intervals in the corridor, drug-induced rotation and stepping tests until Metabolism inhibitor 23 weeks post-lesion. In this experiment the seven unoperated mice were included in all tests as intact controls. The animals were housed under standard conditions with free access to food and water under standard 12-h light–dark regime (light 07.00–19.00 h). All procedures were conducted in accordance with guidelines set by the Ethical Committee for the use of laboratory animals at Lund University. 6-OHDA (Sigma, Sweden) was injected into the substantia nigra (SN) pars compacta under gaseous anaesthesia and analgesia (2% isoflurane in 2 : 1 oxygen/nitrous oxide), using a stereotaxic mouse frame (Stoelting Germany) and a 5-μL Hamilton syringe fitted with a fine glass capillary (external diameter 60–80 μm). The toxin was used at a concentration of 1.