Within-Session Analysis of Amphetamine-Elicited Rotation Behavior Reveals Differences between Young Adult and Middle-Aged F344/BN Rats with Partial Unilateral Striatal Dopamine Depletion

Preclinical modeling of Parkinson's disease using 6-hydroxydopamine (6-OHDA) has been valuable in developing and testing therapeutic strategies. Recent efforts have focused on modeling early stages of disease by infusing 6-OHDA into the striatum. The partial DA depletion that follows intrastriatal 6-OHDA is more variable than the near complete depletion following medial forebrain bundle infusion, and behavioral screening assays are not as well characterized in the partial lesion model. We compared relationships between amphetamine-elicited rotation behavior and DA depletion following intrastriatal 6-OHDA (12.5 μg) in 6 month vs. 18 month F344/BN rats, at 2-weeks and 6-weeks post-lesion. We compared the total number of rotations with within-session (bin-by-bin) parameters of rotation behavior as indicators of DA depletion. Striatal DA depletion was greater in the young adult than in the middle-aged rats at 2 weeks but not at 6 weeks post-lesion. The total number of rotations for the whole session and striatal DA depletion did not differ between the two age groups. Regression analysis revealed a greater relationship between within-session parameters of rotation behavior and DA depletion in the middle-aged group than in the young adult group. These results have implications for estimating DA depletion in preclinical studies using rats of different ages