Figure 1
Chronic l-DOPA treatment impairs motor and cognitive function. Timeline of experimental events in Experiments 1 (A) and 2 (B). (C) In Experiment 1, rats were given dopamine depleting lesions of the MFB, resulting in loss of TH + neurons in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA). No differences in cell loss were observed between saline and l-DOPA treated groups in either subregion (ps = n.s.) (D) Rats exposed to chronic l-DOPA developed AIMS, while rats given saline injections did not develop AIMs. (H) Representative histology of an intact and a 6-OHDA MFB lesion rat, show immunostaining for tyrosine hydroxylase (TH) in the striatum and midbrain illustrating the extent of the lesion. Rats were tested in the lateralised choice reaction time (LCRT) task to assess cognitive function (accuracy), motor speed (movement time) and the time to react to the stimulus onset (reaction time). Overall, rats with MFB lesions showed impaired accuracy ((E); Group: F1,40 = 220.74, p < 0.001), slower motor responses ((F); Group: F1,40 = 43.19, p < 0.001) and slower reaction times ((G); Group: F1,40 = 9.82, p < 0.01) than intact rats. Lesioned rats treated with l-DOPA were significantly more impaired cognitively than saline treated rats (Group*Drug: F1,40 = 4.13, p < 0.05; Lesion rats, saline vs l-DOPA, p < 0.01) and had slower motor responses (Group*Drug: F1,40 = 4.56, p < 0.05; Lesion rats, saline vs l-DOPA, p = 0.001). (I) In Experiment 2, no differences in TH + cell loss were evident between saline, l-DOPA or BRC treated rats in either the SNpc (p = n.s.) or the VTA (p = n.s.). (J) Rats treated chronically with l-DOPA developed AIMs, while rats treated with saline or the D2 agonist BRC did not develop AIMs. The behaviour of intact rats treated with saline, l-DOPA or BRC did not differ on any measure, therefore rats were combined into a single control group. Rats with MFB lesions showed impaired accuracy ((K); Group: F3,81 = 73.11, P < 0.001; Intact vs all lesion groups, ps < 0.001) and motor responses ((L) Group: F3,81 = 30.44; Intact vs all lesion groups, ps < 0.001). After chronic drug treatment, only l-DOPA treated rats showed further impairment in accuracy ((K); l-DOPA vs Saline/BRC, ps < 0.001), motor response ((L); l-DOPA vs Saline/BRC, ps < 0.001) and reaction time ((M); Group: F3,81 = 4.17, p < 0.01; Intact vs l-DOPA, p < 0.01). In contrast, treatment with BRC had no impact on any aspect of task performance relative to saline control. *p < 0.05, **p < 0.01, ***p < 0.001, n.s. = non-significant.
