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

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2010-10, Vol.96 (4), p.423-428
• Main Authors: Bethel-Brown, Crystal S., Zhang, Hongyu, Fowler, Stephen C., Chertoff, Mark E., Watson, G. Stennis, Stanford, John A.
• Format: Article
• Language: English
• Subjects: 3,4-Dihydroxyphenylacetic Acid - metabolism; Adult and adolescent clinical studies; Age Factors; Amphetamine; Amphetamines - pharmacology; Animal models; Animals; Basal ganglia; Behavior, Animal - drug effects; Behavioral assay; Biological and medical sciences; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dopamine - metabolism; Medical sciences; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Neuropharmacology; Organic mental disorders. Neuropsychology; Oxidopamine - pharmacology; Parkinson's disease; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Rats; Rats, Inbred F344; Rotation; Striatum
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2010.06.014

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.