Central nicotinic receptor agonists ABT-418, ABT-089, and (–)-nicotine reduce distractibility in adult monkeys

来自 EBSCO

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作者：

MA Prendergast，WJ Jackson，AV Terry，MW Decker，SP Arneric，JJ Buccafusco

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摘要：

Increased distractibility is associated with both Alzheimer's disease and attention deficit disorder. The present study examined the effects of (–)-nicotine and the novel central nicotinic receptor (nAChR) agonists ABT-418 [( S )-3-methyl-2-pyrrolidinyl)isoxazole] and ABT-089 [2-methyl-3-(2-( S )-pyrrolindinylmethoxy)- pyridine dihydrochloride] on the delayed recall accuracy of adult monkeys exposed to distracting stimuli. Unpredictable exposure to a random visual array produced marked decrements in recall accuracy on trials with the shortest delay intervals, reducing the accuracy on these trials by 23.4%. Intramuscular (IM) administration of (–)-nicotine, in doses of 5.4–43.3nmol/kg, attenuated the effect of the distractor, but did not completely prevent it. Both ABT-418 (2.0–16.2nmol/kg, IM) and ABT-089 (16.4–32.8nmol/kg, IM) prevented distractibility, producing increases of 7.5–25.0% in accuracy on trials disrupted by distractor exposure. Further, both compounds also improved accuracy on trials during which distractors were not presented, an effect which was not observed after (–)-nicotine administration. Nicotinic-mediated side effects were not observed following administration of any compound. Thus, nAChR stimulation reduces distractibility in adult monkeys and may, therefore, represent a target for the pharmacologic treatment of disorders associated with susceptibility to distraction. ABT-418 and ABT-089 appear to be particularly useful in this regard, a likely result of their selective agonist activity at nAChRs expressed in the brain.

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关键词：

Key words Cognition Distractibility Nicotine ABT-418 ABT-089 Monkey Delay matching

DOI：

10.1007/s002130050538

被引量：

178

年份：

1998