Differential sensitivity of cranial and limb motor function to nigrostriatal dopamine depletion

• Published in: Behavioural brain research 2013-01, Vol.237, p.157-163
• Main Authors: Plowman, Emily K., Maling, Nicholas, Rivera, Benjamin J., Larson, Krista, Thomas, Nagheme J., Fowler, Stephen C., Manfredsson, Fredric P., Shrivastav, Rahul, Kleim, Jeffrey A.
• Format: Article
• Language: English
• Subjects: 6-Hydroxydopamine; Adult and adolescent clinical studies; Analysis of Variance; Animals; Behavioral psychophysiology; Biological and medical sciences; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Cranial motor; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Densitometry; Dopamine - deficiency; Extremities - physiopathology; Feeding Behavior - drug effects; Functional Laterality; Fundamental and applied biological sciences. Psychology; Helianthus; Licking; Limb motor; Male; Medical sciences; Motor Activity - drug effects; Motor Activity - physiology; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Organic mental disorders. Neuropsychology; Oxidopamine - pharmacology; Parkinson's disease; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychomotor Performance - drug effects; Psychopathology. Psychiatry; Rats; Rats, Long-Evans; Reaching; Rodent; Substantia Nigra - drug effects; Substantia Nigra - metabolism; Sympatholytics - pharmacology; Tyrosine 3-Monooxygenase - metabolism
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2012.09.031

► Unilateral dopamine depletion impairs limb and cranial motor function. ► Limb motor impairments are more severe than cranial motor impairments. ► Only limb motor function was correlated to degree of dopamine depletion. ► Suggesting differential sensitivities to dopamine depletion in a rodent model of PD. The present study determined the differential effects of unilateral striatal dopamine depletion on cranial motor versus limb motor function. Forty male Long Evans rats were first trained on a comprehensive motor testing battery that dissociated cranial versus limb motor function and included: cylinder forepaw placement, single pellet reaching, vermicelli pasta handling; sunflower seed opening, pasta biting acoustics, and a licking task. Following baseline testing, animals were randomized to either a 6-hydroxydopamine (6-OHDA) (n=20) or control (n=20) group. Animals in the 6-OHDA group received unilateral intrastriatal 6-OHDA infusions to induce striatal dopamine depletion. Six-weeks following infusion, all animals were re-tested on the same battery of motor tests. Near infrared densitometry was performed on sections taken through the striatum that were immunohistochemically stained for tyrosine hydroxylase (TH). Animals in the 6-OHDA condition showed a mean reduction in TH staining of 88.27%. Although 6-OHDA animals were significantly impaired on all motor tasks, limb motor deficits were more severe than cranial motor impairments. Further, performance on limb motor tasks was correlated with degree of TH depletion while performance on cranial motor impairments showed no significant correlation. These results suggest that limb motor function may be more sensitive to striatal dopaminergic depletion than cranial motor function and is consistent with the clinical observation that therapies targeting the nigrostriatal dopaminergic system in Parkinson's disease are more effective for limb motor symptoms than cranial motor impairments.