Abstract：
:Clinical studies have reported that the nicotinic receptor agonist varenicline improves balance and coordination in patients with several types of ataxia, but confirmation in an animal model has not been demonstrated. This study investigated whether varenicline and nicotine could attenuate the ataxia induced in rats following destruction of the olivocerebellar pathway by the neurotoxin 3-acetylpyridine (3-AP). The administration of 3-AP (70 mg/kg followed by 300 mg niacinamide/kg; i.p.) led to an 85% loss of inferior olivary neurons within one week without evidence of recovery, and was accompanied by a 72% decrease in rotorod activity, a 3-fold increase in the time to traverse a stationary beam, a 19% decrease in velocity and 31% decrease in distance moved in the open field, and alterations in gait parameters, with a 19% increase in hindpaw stride width. The daily administration of nicotine (0.33 mg free base/kg) for one week improved rotorod performance by 50% and normalized the increased hindpaw stride width, effects that were prevented by the daily preadministration of the nicotinic antagonist mecamylamine (0.8 mg free base/kg). Varenicline (1 and 3 mg free base/kg daily) also improved rotorod performance by approximately 50% following one week of administration, and although it did not alter the time to traverse the beam, it did improve the ability to maintain balance on the beam. Neither varenicline nor nicotine, at doses that improved balance, affected impaired locomotor activity in the open field. Results provide evidence that nicotinic agonists are of benefit for alleviating some of the behavioral deficits in olivocerebellar ataxia and warrant further studies to elucidate the specific mechanism(s) involved.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Wecker L,Engberg ME,Philpot RM,Lambert CS,Kang CW,Antilla JC,Bickford PC,Hudson CE,Zesiewicz TA,Rowell PPdoi
10.1016/j.neuropharm.2013.05.016subject
Has Abstractpub_date
2013-10-01 00:00:00pages
75-86eissn
0028-3908issn
1873-7064pii
S0028-3908(13)00226-8journal_volume
73pub_type
杂志文章abstract：:The role of the stress-induced increase in the uptake of tryptophan in brain in opioid-induced analgesia was investigated by modifying the uptake of amino acid in brain with injections of competing amino acids. Blockade of analgesia by valine (200 mg/kg, i.p.) alone, and by valine and tyrosine (100 mg/kg, i.p.), but n...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(85)90185-6
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
pub_type： 杂志文章,评审
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
pub_type： 杂志文章
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更新日期：2013-02-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2007.12.005
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journal_title：Neuropharmacology
pub_type： 杂志文章
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journal_title：Neuropharmacology
pub_type： 杂志文章
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journal_title：Neuropharmacology
pub_type： 杂志文章
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pub_type： 杂志文章
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更新日期：2014-07-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(85)90188-1
更新日期：1985-11-01 00:00:00
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journal_title：Neuropharmacology
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pub_type： 杂志文章
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更新日期：2016-12-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2012.04.013
更新日期：2013-05-01 00:00:00
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
pub_type： 杂志文章,评审
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更新日期：2016-07-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
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更新日期：2001-03-01 00:00:00
abstract：:The effects of (S)-4-amino-5-[(4,4-dimethylcyclohexyl)amino]-5-oxo-pentanoic acid ((S)CR 2249), a new chemical entity selected among a series of glutamic acid derivatives, were investigated on N-methyl-D-aspartate (NMDA)-evoked release of [3H]noradrenaline from rat hippocampal slices. (S)CR 2249 facilitated glycine-me...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(97)00092-0
更新日期：1997-08-01 00:00:00
