Atomoxetine improves memory and other components of executive function in young-adult rats and aged rhesus monkeys

Research output: Contribution to journalArticle

Abstract

Atomoxetine is a norepinephrine reuptake inhibitor and FDA-approved treatment for attention deficit/hyperactivity disorder (ADHD)in children, adolescents, and adults. While there is some evidence that atomoxetine may improve additional domains of cognition beyond attention in both young adults and aged individuals, this subject has not been extensively investigated. Here, we evaluated atomoxetine (in low mg/kg doses)in a variable stimulus duration (vSD)and a variable intertrial interval (vITI)version of the five choice-serial reaction time task (5C-SRTT), and an eight-arm radial arm maze (RAM)procedure in young-adult rats. The compound was further evaluated (in μg/kg-low mg/kg doses)along with nicotine (as a reference compound)and the Alzheimer's disease treatment donepezil in a distractor version of a delayed match to sample task (DMTS-D)in aged monkeys (mean age = 21.8 years). Atomoxetine (depending on the dose)improved accuracy (sustained attention)as well as behaviors related to impulsivity, compulsivity and cognitive inflexibility in both the vSD and vITI tasks and it improved spatial reference memory in the RAM. In the DMTS-D task, both nicotine and atomoxetine, but not donepezil attenuated the effects of the distractor on accuracy at short delays (non-spatial working/short term memory). However, combining sub-effective doses of atomoxetine and donepezil did enhance DMTS-D accuracy indicating the potential of using atomoxetine as an adjunctive treatment with donepezil. Collectively, these animal studies support the further evaluation of atomoxetine as a repurposed drug for younger adults as well older individuals who suffer from deficits in attention, memory and other components of executive function.

Original languageEnglish (US)
Pages (from-to)65-75
Number of pages11
JournalNeuropharmacology
Volume155
DOIs
StatePublished - Sep 1 2019

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Executive Function
Macaca mulatta
Young Adult
Nicotine
Drug Repositioning
Atomoxetine Hydrochloride
Impulsive Behavior
Attention Deficit Disorder with Hyperactivity
Short-Term Memory
Cognition
Reaction Time
Haplorhini
Norepinephrine
Alzheimer Disease
Therapeutics
donepezil

Keywords

  • Attention
  • Cholinergic
  • Cognitive flexibility
  • Dementia
  • Distractibility
  • Noradrenergic

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

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title = "Atomoxetine improves memory and other components of executive function in young-adult rats and aged rhesus monkeys",
abstract = "Atomoxetine is a norepinephrine reuptake inhibitor and FDA-approved treatment for attention deficit/hyperactivity disorder (ADHD)in children, adolescents, and adults. While there is some evidence that atomoxetine may improve additional domains of cognition beyond attention in both young adults and aged individuals, this subject has not been extensively investigated. Here, we evaluated atomoxetine (in low mg/kg doses)in a variable stimulus duration (vSD)and a variable intertrial interval (vITI)version of the five choice-serial reaction time task (5C-SRTT), and an eight-arm radial arm maze (RAM)procedure in young-adult rats. The compound was further evaluated (in μg/kg-low mg/kg doses)along with nicotine (as a reference compound)and the Alzheimer's disease treatment donepezil in a distractor version of a delayed match to sample task (DMTS-D)in aged monkeys (mean age = 21.8 years). Atomoxetine (depending on the dose)improved accuracy (sustained attention)as well as behaviors related to impulsivity, compulsivity and cognitive inflexibility in both the vSD and vITI tasks and it improved spatial reference memory in the RAM. In the DMTS-D task, both nicotine and atomoxetine, but not donepezil attenuated the effects of the distractor on accuracy at short delays (non-spatial working/short term memory). However, combining sub-effective doses of atomoxetine and donepezil did enhance DMTS-D accuracy indicating the potential of using atomoxetine as an adjunctive treatment with donepezil. Collectively, these animal studies support the further evaluation of atomoxetine as a repurposed drug for younger adults as well older individuals who suffer from deficits in attention, memory and other components of executive function.",
keywords = "Attention, Cholinergic, Cognitive flexibility, Dementia, Distractibility, Noradrenergic",
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T1 - Atomoxetine improves memory and other components of executive function in young-adult rats and aged rhesus monkeys

AU - Callahan, Patrick Michael

AU - Plagenhoef, Marc R.

AU - Blake, David Trumbull

AU - Terry, Alvin V

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N2 - Atomoxetine is a norepinephrine reuptake inhibitor and FDA-approved treatment for attention deficit/hyperactivity disorder (ADHD)in children, adolescents, and adults. While there is some evidence that atomoxetine may improve additional domains of cognition beyond attention in both young adults and aged individuals, this subject has not been extensively investigated. Here, we evaluated atomoxetine (in low mg/kg doses)in a variable stimulus duration (vSD)and a variable intertrial interval (vITI)version of the five choice-serial reaction time task (5C-SRTT), and an eight-arm radial arm maze (RAM)procedure in young-adult rats. The compound was further evaluated (in μg/kg-low mg/kg doses)along with nicotine (as a reference compound)and the Alzheimer's disease treatment donepezil in a distractor version of a delayed match to sample task (DMTS-D)in aged monkeys (mean age = 21.8 years). Atomoxetine (depending on the dose)improved accuracy (sustained attention)as well as behaviors related to impulsivity, compulsivity and cognitive inflexibility in both the vSD and vITI tasks and it improved spatial reference memory in the RAM. In the DMTS-D task, both nicotine and atomoxetine, but not donepezil attenuated the effects of the distractor on accuracy at short delays (non-spatial working/short term memory). However, combining sub-effective doses of atomoxetine and donepezil did enhance DMTS-D accuracy indicating the potential of using atomoxetine as an adjunctive treatment with donepezil. Collectively, these animal studies support the further evaluation of atomoxetine as a repurposed drug for younger adults as well older individuals who suffer from deficits in attention, memory and other components of executive function.

AB - Atomoxetine is a norepinephrine reuptake inhibitor and FDA-approved treatment for attention deficit/hyperactivity disorder (ADHD)in children, adolescents, and adults. While there is some evidence that atomoxetine may improve additional domains of cognition beyond attention in both young adults and aged individuals, this subject has not been extensively investigated. Here, we evaluated atomoxetine (in low mg/kg doses)in a variable stimulus duration (vSD)and a variable intertrial interval (vITI)version of the five choice-serial reaction time task (5C-SRTT), and an eight-arm radial arm maze (RAM)procedure in young-adult rats. The compound was further evaluated (in μg/kg-low mg/kg doses)along with nicotine (as a reference compound)and the Alzheimer's disease treatment donepezil in a distractor version of a delayed match to sample task (DMTS-D)in aged monkeys (mean age = 21.8 years). Atomoxetine (depending on the dose)improved accuracy (sustained attention)as well as behaviors related to impulsivity, compulsivity and cognitive inflexibility in both the vSD and vITI tasks and it improved spatial reference memory in the RAM. In the DMTS-D task, both nicotine and atomoxetine, but not donepezil attenuated the effects of the distractor on accuracy at short delays (non-spatial working/short term memory). However, combining sub-effective doses of atomoxetine and donepezil did enhance DMTS-D accuracy indicating the potential of using atomoxetine as an adjunctive treatment with donepezil. Collectively, these animal studies support the further evaluation of atomoxetine as a repurposed drug for younger adults as well older individuals who suffer from deficits in attention, memory and other components of executive function.

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