title: 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.
abstract: 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 microg) 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.
authors.affiliation: Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Crystal S
authors.initials: CS
authors.lastname: Bethel-Brown
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Fowler
authors.forename: Mark E
authors.initials: ME
authors.lastname: Chertoff
authors.forename: G Stennis
authors.initials: GS
authors.lastname: Watson
authors.forename: John A
authors.initials: JA
authors.lastname: Stanford
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000367:Age Factors; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000662:Amphetamines; D015102:3,4-Dihydroxyphenylacetic Acid; D016627:Oxidopamine; D004298:Dopamine