Figure 4. Effect of strain on baseline and treatment levels of monoamine tissue content and extracellular levels in the lesioned striatum, as well as on LID behaviors and levodopa-induced rotations in levodopa primed F344 and Lewis rats.

A-C) Tissue content of DA and 5HT in intact and lesioned striatum. As depicted in Figure 3A, F344 and Lewis rats from cohort #1 (Exp. 3a) were sacrificed for HPLC determination of tissue content of DA, DOPAC and 5HT 120 mins after levodopa (LD, 12mg/kg, N=6) or the vehicle saline (Veh, N=4). Data represent mean ± SEM and was analyzed with two-way ANOVA and post-hoc Tukey’s HSD test (A, B,) or two-tailed unpaired t-test (C). D) Relationship of DA and 5HT content in the lesioned striatum to dyskinesias severity between F344 and Lewis. There is a positive correlation of increasing LID severity with increasing striatal DA content in F344 (r²=0.749; p=0.02), but not in Lewis rats. In contrast there is an inverse correlation of LID severity with 5HT content in Lewis (r²=0.758; p=0.02), but not in F344 rats. Data were analyzed with best-fit linear regression and non-parametric Spearman correlation analyses. Best-fit linear regression: values shown in graph; Spearman correlation: Lewis (N=6) 5HT p=0.0056, DA p=0.2722; F344 (N=6) 5HT p=0.0667, DA p=0.050. E-L) Extracellular monoamine levels. As detailed in Figure 3A, rats from cohort #2 (Exp. 3b) were tested using in vivo microdialysis where, after a 1 hr habituation, striatal dialysate samples were collected every 20 min for a total of 18 samples. Rats were injected with the levodopa vehicle (saline) 10 min prior to baseline (B1 – 9) and again with levodopa (6 mg/kg; arrow) 10 mins prior to treatment time point sampling (T1 – 9). Monoamine levels (mean ± SEM) are presented as percent change from baseline (E, G, I) and pmol (F, H, J). Differences in strain, treatment (baseline vs levodopa), time, and strain x treatment x time (2 × 2 × 9) interactions with 3-way ANOVAs. All significant ANOVA effects were further analyzed using Tukey HSD post-hoc tests. K) LID behaviors and rotations were rated every 20 mins just prior to dialysate collection. LID data are presented as medians ± median absolute deviation (MAD) and were analyzed for strain differences using Mann Whitney U tests at each time point. L) Levodopa-induced rotations are presented as means ± SEM and were analyzed for differences in strain, time, and strain x time (2 × 9) interactions with 2-way ANOVAs. Statistical indications: E, F: vs corresponding Baseline time point; K: F344 vs. Lewis; L: vs. T1.