Impaired acquisition of skilled behavior in rotarod task by moderate depletion of striatal dopamine in a pre-symptomatic stage model of Parkinson's disease

• Published in: Neuroscience research Vol. 51; no. 3; pp. 299 - 308
• Main Authors: Ogura, Taichi, Ogata, Masanori, Akita, Hisanao, Jitsuki, Susumu, Akiba, Lisa, Noda, Kazuko, Hoka, Sumio, Saji, Makoto
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.03.2005
• Subjects: 6-OHDA-induced lesion; Acquisition of skilled behavior; Amphetamine - pharmacology; Animals; Behavior, Animal; Cell Count - methods; Cell Survival - drug effects; Central Nervous System Stimulants - pharmacology; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Disease Models, Animal; Dopamine - deficiency; Exploratory Behavior - drug effects; Functional Laterality; Hindlimb Suspension - methods; Immunohistochemistry - methods; Male; Medial Forebrain Bundle - drug effects; Medial Forebrain Bundle - metabolism; Microdialysis - methods; Microdialysis method; Motor Activity - drug effects; Motor Activity - physiology; Motor functions; Motor Skills - physiology; Oxidopamine - toxicity; Parkinson Disease - etiology; Parkinson Disease - metabolism; Parkinson Disease - physiopathology; Rats; Rats, Wistar; Regression Analysis; Rotarod Performance Test - methods; Rotarod test; Substantia Nigra - drug effects; Substantia Nigra - metabolism; Sympatholytics - toxicity; Time Factors; Tyrosine 3-Monooxygenase - metabolism; Rotarod test; Acquisition of skilled behavior; Motor functions; 6-OHDA-induced lesion; Microdialysis method
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/j.neures.2004.12.006

In view of recent findings that suggest that the nigrostriatal dopamine (DA) system plays a role in motor control and the acquisition of habits and skills, we hypothesized that the striatum-based function underlying the acquisition of skilled behaviors might be more vulnerable to dopamine depletion than the motor control. To test this hypothesis, we investigated whether impaired acquisition of skilled behaviors occurs in a pre-symptomatic stage model of Parkinson's disease (PD). By using the microdialysis method and the 6-OHDA-technique to destroy dopamine neurons, we confirmed that rats with unilateral partial lesions of the nigral dopamine cells by 6-OHDA are suitable for a pre-symptomatic stage model of Parkinson's disease. The rats in this model exhibited moderate disruption of striatal dopamine release function and relatively intact motor functions. In a rotarod test, the impaired acquisition of skilled behavior occurred in rats with bilateral partial lesions of the nigral dopamine cells by 6-OHDA. These rats displayed intact general motor functions, such as locomotor activity, adjusting steps, equilibrium function and muscle strength. Based on these results, we concluded that the striatum-based function underlying the acquisition of skilled behaviors or sensorimotor learning may be more vulnerable to dopamine depletion than the motor control.