Differential effects of D1 and D2 dopamine agonists on memory, motivation, learning and response time in non‐human primates

Dopamine (DA) plays a critical role in cognition, motivation and information processing. DA action has been shown to both improve and/or impair cognition across different receptor types, species, subjects and tasks. This complex relationship has been described as an inverted U‐shaped function and ma...

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Bibliographic Details
Published in:The European journal of neuroscience 2019-01, Vol.49 (2), p.199-214
Main Authors: Marino, Robert A., Levy, Ron
Format: Article
Language:English
Subjects:
Agonists
Animals
Associative learning
attention
Benzimidazoles - administration & dosage
CANTAB
Cognition & reasoning
Cognitive ability
Dopamine
Dopamine Agonists - administration & dosage
Dopamine D1 receptors
Dopamine D2 receptors
Dopamine receptors
Dosage
Information processing
Latency
learning
Learning - drug effects
Learning - physiology
Macaca mulatta
Male
Memory
Memory - drug effects
Memory - physiology
Mental task performance
Motivation
Motivation - drug effects
Motivation - physiology
Motor task performance
Neostriatum
Neuropsychological Tests
Phenanthridines - administration & dosage
Prefrontal cortex
Psychomotor Performance - drug effects
Psychomotor Performance - physiology
reaching
Reaction time task
Receptor mechanisms
Receptors, Dopamine D1 - agonists
Receptors, Dopamine D1 - physiology
Receptors, Dopamine D2 - agonists
Receptors, Dopamine D2 - physiology
Reversal learning
Short term memory
Spatial memory
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Summary:Dopamine (DA) plays a critical role in cognition, motivation and information processing. DA action has been shown to both improve and/or impair cognition across different receptor types, species, subjects and tasks. This complex relationship has been described as an inverted U‐shaped function and may be due to the differential effects of DA receptor activation in the striatum and prefrontal cortex. We have investigated the effects of selective DA agonists on cognitive performance in healthy monkeys using a touch screen running tasks from the CAmbridge Neuropsychological Test Automated Battery (CANTAB). One of two DA agonist drugs or placebo was administered prior to each daily CANTAB session: Dihydrexidine hydrochloride (selective D1 agonist, 0.4–0.9 mg/kg), or sumanirole maleate (selective D2 agonist 0.05–0.3 mg/kg). Three CANTAB tasks were tested: (a) “self‐ordered sequential search task” which tested spatial working memory, (b) “reversal learning task,” which tested association learning, cognitive flexibility and attention and (c) “visually guided reaching task,” which tested reaction time and accuracy. At high dosages, the D2 agonist improved spatial working memory performance, while impairing reversal learning and slowing reach response latency. No consistent cognitive effects were observed with the D1 agonist across the dosages tested. A significant decrease in trial completion rate was observed at the higher dosages of both the D1 and D2 agonists which were consistent with decreased motivation. These results are consistent with task‐specific effects of a D2 agonist as well as dose specific insensitivities of a D1 agonist on cognitive and motor behaviors in a healthy monkey.
ISSN:0953-816X
1460-9568
DOI:10.1111/ejn.14208