Abstract
Clinical data indicate that the neuronal nicotinic acetylcholine receptor (nAChR) partial agonist varenicline ameliorates abnormalities in gait and balance in patients with spinocerebellar ataxia type 3, but the mechanisms involved have not been investigated. The goal of this study was to determine whether nicotine (Nic) could improve gait in an animal model of ataxia and whether this effect was mediated by an action at nAChRs. Following baseline assessment of locomotor activity and gait, male Sprague‐Dawley rats received injections of the neurotoxin 3‐acetylpyridine (3‐AP) to preferentially destroy the olivocerebellar pathway, and behaviors were reassessed one week later. Subsequently, animals received daily injections of either saline or mecamylamine (Mec, 1 mg/kg), followed 30 minutes later by either saline or Nic (1 mg/kg) for 1 week. The administration of 3‐ AP led to a 21–23% decrease in distance moved and velocity of movement, an 8% decrease in hindpaw stride length and a 25% increase stride width. Nic administration for 1 week did not alter locomotor activity or velocity, but did improve hindpaw stride length and width, effects that were prevented by prior Mec administration. Results indicate that activation of nAChRs is of benefit in an animal model of olivocerebellar degeneration. Current experiments are determining the specific nAChRs involved and the cellular mechanism mediating this effect. Supported by NIH #NS072114‐01
Published Version
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