Figure 1.

Experimental design. At the onset of the experiment, 60 animals received a unilateral 6-OHDA lesion of the medial forebrain bundle (MFB) in order to obtain a complete lesion of the nigrostriatal dopamine pathway. Thirty-four animals that displayed more than six full-body turns per minute, towards the lesioned side, in the d-amphetamine (Amph)-induced rotation test were selected for further analysis in a battery of motor tests. At 6 weeks post-lesion, the animals were balanced into three treatment groups on the basis of performance in stepping, cylinder and the apomorphine (Apo)- and amphetamine-induced rotation tests to receive either the two vector mix (TH + GCH1 group, n = 14) or only the control vector (GCH1 only group, n = 8), or be treated as non-vector-injected lesion controls (Les-Sham group, n = 12). A fourth group with intact animals (n = 5) was included in the experiment as a non-lesioned control group in the l-DOPA-induced dyskinesia test. Over the 6 months that followed, the animals were tested repeatedly using the different motor tests. At Week 15 post-transduction, daily peripheral l-DOPA administration was initiated, and abnormal involuntary movement (AIM) scoring was conducted on treatment Days 1, 4, 8, 12 and 16. At Week 23, sub-groups of the TH + GCH1 group (n = 5) and the Les-Sham group (n = 5) were tested in the stepping and cylinder tests, whereafter they received a unilateral injection of 5,7-DHT into the medial forebrain bundle. At week 26, the same animals were re-tested in the two tests. All animals were killed for biochemical analysis at 28 weeks after vector delivery.