title: Analysis of gait in rats with olivocerebellar lesions and ability of the nicotinic acetylcholine receptor agonist varenicline to attenuate impairments.
abstract: Studies have demonstrated that administration of the neuronal nicotinic receptor agonist varenicline to rats with olivocerebellar lesions attenuates balance deficits on a rotorod and balance beam, but the effects of this drug on gait deficits have not been investigated. To accomplish this, male Sprague-Dawley rats were trained to walk on a motorized treadmill at 25 and 35 cm/s and baseline performance determined; both temporal and spatial gait parameters were analyzed. A principal component analysis (PCA) was used to identify the key components of gait, and the cumulative gait index (CGI) was calculated, representing deviations from prototypical gait patterns. Subsequently, animals either remained as non-lesioned controls or received injections of 3-acetylpyridine (3-AP)/nicotinamide to destroy the climbing fibers innervating Purkinje cells. The gait of the non-lesioned group was assessed weekly to monitor changes in the normal population, while the gait of the lesioned group was assessed 1 week following 3-AP administration, and weekly following the daily administration of saline or varenicline (0.3, 1.0, or 3.0mg free base/kg) for 2 weeks. Non-lesioned animals exhibited a 60-70% increased CGI over time due to increases in temporal gait measures, whereas lesioned animals exhibited a nearly 3-fold increased CGI as a consequence of increases in spatial measures. Following 2 weeks of treatment with the highest dose of varenicline (3.0mg free base/kg), the swing duration of lesioned animals normalized, and stride duration, stride length and step angle in this population did not differ from the non-lesioned population. Thus, varenicline enabled animals to compensate for their impairments and rectify the timing of the gait cycle.
authors.affiliation: Department of Molecular Pharmacology and Physiology, University of South Florida Morsani College of Medicine, Tampa, FL, USA; Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Neurosciences, University of South Florida Morsani College of Medicine, Tampa, FL, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Lambert
authors.affiliation: Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Neurosciences, University of South Florida Morsani College of Medicine, Tampa, FL, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Philpot
authors.affiliation: Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Neurosciences, University of South Florida Morsani College of Medicine, Tampa, FL, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Engberg
authors.affiliation: Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Neurosciences, University of South Florida Morsani College of Medicine, Tampa, FL, USA.
authors.forename: B E
authors.initials: BE
authors.lastname: Johns
authors.affiliation: Department of Molecular Pharmacology and Physiology, University of South Florida Morsani College of Medicine, Tampa, FL, USA; Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Neurosciences, University of South Florida Morsani College of Medicine, Tampa, FL, USA; Department of Neurology, University of South Florida Morsani College of Medicine, Tampa, FL, USA; School of Physical Therapy and Rehabilitation Sciences, University of South Florida Morsani College of Medicine, Tampa, FL, USA. Electronic address: lwecker@health.usf.edu.
authors.forename: L
authors.initials: L
authors.lastname: Wecker
mesh_terms: D000818:Animals; D001259:Ataxia / Q000188:drug therapy* / Q000503:physiopathology; D001696:Biomechanical Phenomena; D002531:Cerebellum / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005684:Gait / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009536:Niacinamide; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009847:Olivary Nucleus / Q000503:physiopathology; D025341:Principal Component Analysis; D011725:Pyridines; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D000068580:Varenicline / Q000494:pharmacology*; D016138:Walking / Q000502:physiology
chemical_list: D018722:Nicotinic Agonists; D011725:Pyridines; C010835:3-acetylpyridine; D009536:Niacinamide; D000068580:Varenicline
keywords: Ataxia; Cumulative gait index; Gait; Principal component analysis; Varenicline