Enhancement of sustained attention performance by the nicotinic acetylcholine receptor agonist ABT-418 in intact but not basal forebrain-lesioned rats.

Academic Article


  • RATIONALE: Loss of telencephalic cholinergic projections has been postulated to contribute significantly to the cognitive decline associated with aging and dementia. OBJECTIVE: The effects of the nicotinic acetylcholine receptor agonist ABT-418, a potential therapeutic drug for the treatment of the age- and dementia-associated cognitive disorders, were tested in an animal model of the cortical cholinergic deafferentation-induced impairments in sustained attention. METHODS: Animals were trained in an operant task designed to test sustained attention performance. A partial loss of cortical cholinergic inputs was produced by infusions of 192 IgG-saporin into the basal forebrain. The effects of the systemic administration of ABT-418 (0.04, 0.13, 0.39 mg/kg) and the psychostimulant methylphenidate (0.2, 0.4, 0.8 mg/kg) were assessed. RESULTS: Compared with sham-lesioned animals, this lesion resulted in a decrease in the relative number of hits while the relative number of correct rejections remained unaffected. Administration of ABT-418 significantly improved the relative number of hits. Furthermore, this effect of ABT-418 interacted with the effects of the lesion. Unexpectedly, this interaction was based on a significant enhancement of the performance of sham-lesioned animals while no effects were found in 192 IgG-saporin-lesioned animals. Administration of methylphenidate did not affect performance. CONCLUSIONS: While these data do not support the hypothesis that administration of ABT-418 attenuates the impairments in attentional performance that result from loss of cortical cholinergic inputs, they support previous notions about this drug's ability to enhance cognitive processes in intact subjects.
  • Authors

  • McGaughy, Jill
  • Decker, MW
  • Sarter, M
  • Status

    Publication Date

  • May 1999
  • Published In

  • Psychopharmacology  Journal
  • Keywords

  • Animals
  • Attention
  • Behavior, Animal
  • Central Nervous System Stimulants
  • Isoxazoles
  • Male
  • Methylphenidate
  • Nootropic Agents
  • Prosencephalon
  • Pyrrolidines
  • Rats
  • Rats, Inbred F344
  • Receptors, Nicotinic
  • Digital Object Identifier (doi)

    Pubmed Id

  • 10394999
  • Start Page

  • 175
  • End Page

  • 182
  • Volume

  • 144
  • Issue

  • 2