Alpha 2A adrenergic receptor agonist, guanfacine, attenuates cocaine-related impairments of inhibitory response control and working memory in animal models

Alvin V Terry, Patrick Michael Callahan, Rosann Schade, Nancy J. Kille, Marc Plagenhoef

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8 Citations (Scopus)

Abstract

There is considerable evidence that centrally acting α2A adrenergic receptor agonists can attenuate impairments in executive function that result from dysfunction of the prefrontal cortex. Such positive effects resulted in the recent approval by the United States Food and Drug Administration (FDA) of the α2A agonists clonidine and guanfacine for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD), but also suggest that they could have beneficial effects in substance abuse disorders and other neuropsychiatric conditions. The purpose of this study was to evaluate guanfacine for its ability to attenuate behavioral alterations associated with acute cocaine exposure in rats trained to perform a task of sustained attention, the five choice serial reaction time task (5C-SRTT) and monkeys trained to perform a task of working/short term memory, the delayed match to sample (DMTS) task. In the rodent 5C-SRTT acute intraperitoneal (i.p.) administration of cocaine (3.5-15.0 mg/kg) did not affect accuracy, but was associated with dose-dependent increases in premature responses and timeout responses. Guanfacine (0.1-1.0 mg/kg i.p.) dose-dependently decreased premature responses and timeout responses associated with cocaine and it attenuated similar deficits in inhibitory response control observed in a variable ITI version of the 5C-SRTT. In the DMTS task in monkeys, acute intramuscular (i.m.) administration of cocaine (4.0 mg/kg) was associated with impairments in accuracy at long delay intervals, an effect that was attenuated by guanfacine (0.4 mg/kg). These animal studies suggest that guanfacine may have therapeutic potential for treating impairments of executive function that are associated with the abuse of cocaine.

Original languageEnglish (US)
Pages (from-to)63-72
Number of pages10
JournalPharmacology Biochemistry and Behavior
Volume126
DOIs
StatePublished - Jan 1 2014

Fingerprint

Guanfacine
Adrenergic alpha-2 Receptors
Adrenergic alpha-Agonists
Adrenergic Agonists
Cocaine
Short-Term Memory
Animals
Animal Models
Data storage equipment
Executive Function
Haplorhini
Cocaine-Related Disorders
Aptitude
Clonidine
United States Food and Drug Administration
Attention Deficit Disorder with Hyperactivity
Prefrontal Cortex
Reaction Time
Substance-Related Disorders
Rats

Keywords

  • Addiction
  • Cocaine
  • Cognition
  • Compulsivity
  • Drug abuse
  • Executive function
  • Impulsivity

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Pharmacology
  • Toxicology
  • Behavioral Neuroscience
  • Biological Psychiatry
  • Medicine(all)

Cite this

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title = "Alpha 2A adrenergic receptor agonist, guanfacine, attenuates cocaine-related impairments of inhibitory response control and working memory in animal models",
abstract = "There is considerable evidence that centrally acting α2A adrenergic receptor agonists can attenuate impairments in executive function that result from dysfunction of the prefrontal cortex. Such positive effects resulted in the recent approval by the United States Food and Drug Administration (FDA) of the α2A agonists clonidine and guanfacine for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD), but also suggest that they could have beneficial effects in substance abuse disorders and other neuropsychiatric conditions. The purpose of this study was to evaluate guanfacine for its ability to attenuate behavioral alterations associated with acute cocaine exposure in rats trained to perform a task of sustained attention, the five choice serial reaction time task (5C-SRTT) and monkeys trained to perform a task of working/short term memory, the delayed match to sample (DMTS) task. In the rodent 5C-SRTT acute intraperitoneal (i.p.) administration of cocaine (3.5-15.0 mg/kg) did not affect accuracy, but was associated with dose-dependent increases in premature responses and timeout responses. Guanfacine (0.1-1.0 mg/kg i.p.) dose-dependently decreased premature responses and timeout responses associated with cocaine and it attenuated similar deficits in inhibitory response control observed in a variable ITI version of the 5C-SRTT. In the DMTS task in monkeys, acute intramuscular (i.m.) administration of cocaine (4.0 mg/kg) was associated with impairments in accuracy at long delay intervals, an effect that was attenuated by guanfacine (0.4 mg/kg). These animal studies suggest that guanfacine may have therapeutic potential for treating impairments of executive function that are associated with the abuse of cocaine.",
keywords = "Addiction, Cocaine, Cognition, Compulsivity, Drug abuse, Executive function, Impulsivity",
author = "Terry, {Alvin V} and Callahan, {Patrick Michael} and Rosann Schade and Kille, {Nancy J.} and Marc Plagenhoef",
year = "2014",
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T1 - Alpha 2A adrenergic receptor agonist, guanfacine, attenuates cocaine-related impairments of inhibitory response control and working memory in animal models

AU - Terry, Alvin V

AU - Callahan, Patrick Michael

AU - Schade, Rosann

AU - Kille, Nancy J.

AU - Plagenhoef, Marc

PY - 2014/1/1

Y1 - 2014/1/1

N2 - There is considerable evidence that centrally acting α2A adrenergic receptor agonists can attenuate impairments in executive function that result from dysfunction of the prefrontal cortex. Such positive effects resulted in the recent approval by the United States Food and Drug Administration (FDA) of the α2A agonists clonidine and guanfacine for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD), but also suggest that they could have beneficial effects in substance abuse disorders and other neuropsychiatric conditions. The purpose of this study was to evaluate guanfacine for its ability to attenuate behavioral alterations associated with acute cocaine exposure in rats trained to perform a task of sustained attention, the five choice serial reaction time task (5C-SRTT) and monkeys trained to perform a task of working/short term memory, the delayed match to sample (DMTS) task. In the rodent 5C-SRTT acute intraperitoneal (i.p.) administration of cocaine (3.5-15.0 mg/kg) did not affect accuracy, but was associated with dose-dependent increases in premature responses and timeout responses. Guanfacine (0.1-1.0 mg/kg i.p.) dose-dependently decreased premature responses and timeout responses associated with cocaine and it attenuated similar deficits in inhibitory response control observed in a variable ITI version of the 5C-SRTT. In the DMTS task in monkeys, acute intramuscular (i.m.) administration of cocaine (4.0 mg/kg) was associated with impairments in accuracy at long delay intervals, an effect that was attenuated by guanfacine (0.4 mg/kg). These animal studies suggest that guanfacine may have therapeutic potential for treating impairments of executive function that are associated with the abuse of cocaine.

AB - There is considerable evidence that centrally acting α2A adrenergic receptor agonists can attenuate impairments in executive function that result from dysfunction of the prefrontal cortex. Such positive effects resulted in the recent approval by the United States Food and Drug Administration (FDA) of the α2A agonists clonidine and guanfacine for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD), but also suggest that they could have beneficial effects in substance abuse disorders and other neuropsychiatric conditions. The purpose of this study was to evaluate guanfacine for its ability to attenuate behavioral alterations associated with acute cocaine exposure in rats trained to perform a task of sustained attention, the five choice serial reaction time task (5C-SRTT) and monkeys trained to perform a task of working/short term memory, the delayed match to sample (DMTS) task. In the rodent 5C-SRTT acute intraperitoneal (i.p.) administration of cocaine (3.5-15.0 mg/kg) did not affect accuracy, but was associated with dose-dependent increases in premature responses and timeout responses. Guanfacine (0.1-1.0 mg/kg i.p.) dose-dependently decreased premature responses and timeout responses associated with cocaine and it attenuated similar deficits in inhibitory response control observed in a variable ITI version of the 5C-SRTT. In the DMTS task in monkeys, acute intramuscular (i.m.) administration of cocaine (4.0 mg/kg) was associated with impairments in accuracy at long delay intervals, an effect that was attenuated by guanfacine (0.4 mg/kg). These animal studies suggest that guanfacine may have therapeutic potential for treating impairments of executive function that are associated with the abuse of cocaine.

KW - Addiction

KW - Cocaine

KW - Cognition

KW - Compulsivity

KW - Drug abuse

KW - Executive function

KW - Impulsivity

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JO - Pharmacology Biochemistry and Behavior

JF - Pharmacology Biochemistry and Behavior

SN - 0091-3057

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