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

Mark A. Prendergast, William J. Jackson, Alvin V Terry, Michael W. Decker, Stephen P. Arneric, Jerry J. Buccafusco

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

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-metoyl-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 5.4-43.3 nmol/kg, attenuated the effect of the distractor, but did not completely prevent it. Both ABT-418 (2.0-16.2 nmol/kg, IM) and ABT-089 (16.4-32.8 nmol/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.

Original languageEnglish (US)
Pages (from-to)50-58
Number of pages9
JournalPsychopharmacology
Volume136
Issue number1
DOIs
StatePublished - Jan 1 1998

Fingerprint

Nicotinic Agonists
Nicotinic Receptors
Nicotine
Haplorhini
Isoxazoles
Attention Deficit Disorder with Hyperactivity
Alzheimer Disease
Brain
3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole
pozanicline

Keywords

  • (-)-Nicotine
  • ABT-089
  • ABT-418
  • Cognition
  • Delay matching
  • Distractibility
  • Monkey

ASJC Scopus subject areas

  • Pharmacology

Cite this

Central nicotinic receptor agonists ABT-418, ABT-089, and (-)-nicotine reduce distractibility in adult monkeys. / Prendergast, Mark A.; Jackson, William J.; Terry, Alvin V; Decker, Michael W.; Arneric, Stephen P.; Buccafusco, Jerry J.

In: Psychopharmacology, Vol. 136, No. 1, 01.01.1998, p. 50-58.

Research output: Contribution to journalArticle

Prendergast, Mark A. ; Jackson, William J. ; Terry, Alvin V ; Decker, Michael W. ; Arneric, Stephen P. ; Buccafusco, Jerry J. / Central nicotinic receptor agonists ABT-418, ABT-089, and (-)-nicotine reduce distractibility in adult monkeys. In: Psychopharmacology. 1998 ; Vol. 136, No. 1. pp. 50-58.
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