The Effects of a Novel Non-catechol Dopamine Partial Agonist on Working Memory in the Aged Rhesus Monkey

Aged-related declines in cognition, especially working memory and executive function, begin in middle-age and these abilities are known to be mediated by the prefrontal cortex (PFC) and more specifically the dopamine (DA) system within the PFC. In both humans and monkeys, there is significant eviden...

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Autores principales:	Tara L. Moore, Damon A. Young, Ronald J. Killiany, Kari R. Fonseca, Dmitri Volfson, David L. Gray, Rita Balice-Gordon, Rouba Kozak
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	dopamine aging prefrontal cortex rhesus monkey memory Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/de9abf602a974353b8531c96d2cb9afe
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spelling	oai:doaj.org-article:de9abf602a974353b8531c96d2cb9afe2021-12-01T07:46:03ZThe Effects of a Novel Non-catechol Dopamine Partial Agonist on Working Memory in the Aged Rhesus Monkey1663-436510.3389/fnagi.2021.757850https://doaj.org/article/de9abf602a974353b8531c96d2cb9afe2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnagi.2021.757850/fullhttps://doaj.org/toc/1663-4365Aged-related declines in cognition, especially working memory and executive function, begin in middle-age and these abilities are known to be mediated by the prefrontal cortex (PFC) and more specifically the dopamine (DA) system within the PFC. In both humans and monkeys, there is significant evidence that the PFC is the first cortical region to change with age and the PFC appears to be particularly vulnerable to age-related loss of dopamine (DA). Therefore, the DA system is a strong candidate for therapeutic intervention to slow or reverse age related declines in cognition. In the present study, we administered a novel selective, potent, non-catechol DA D1 R agonist PF-6294 (Pfizer, Inc.) to aged female rhesus monkeys and assessed their performance on two benchmark tasks of working memory – the Delayed Non-match to Sample Task (DNMS) and Delayed Recognition Span Task (DRST). The DNMS task was administered first with the standard 10 s delay and then with 5 min delays, with and without distractors. The DRST was administered each day with four trials with unique sequences and one trial of a repeated sequence to assess evidence learning and retention. Overall, there was no significant effect of drug on performance on any aspect of the DNMS task. In contrast, we demonstrated that a middle range dose of PF-6294 significantly increased memory span on the DRST on the first and last days of testing and by the last day of testing the increased memory span was driven by the performance on the repeated trials.Tara L. MooreTara L. MooreDamon A. YoungRonald J. KillianyRonald J. KillianyKari R. FonsecaDmitri VolfsonDavid L. GrayRita Balice-GordonRouba KozakFrontiers Media S.A.articledopamineagingprefrontal cortexrhesus monkeymemoryNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Aging Neuroscience, Vol 13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	dopamine aging prefrontal cortex rhesus monkey memory Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	dopamine aging prefrontal cortex rhesus monkey memory Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Tara L. Moore Tara L. Moore Damon A. Young Ronald J. Killiany Ronald J. Killiany Kari R. Fonseca Dmitri Volfson David L. Gray Rita Balice-Gordon Rouba Kozak The Effects of a Novel Non-catechol Dopamine Partial Agonist on Working Memory in the Aged Rhesus Monkey
description	Aged-related declines in cognition, especially working memory and executive function, begin in middle-age and these abilities are known to be mediated by the prefrontal cortex (PFC) and more specifically the dopamine (DA) system within the PFC. In both humans and monkeys, there is significant evidence that the PFC is the first cortical region to change with age and the PFC appears to be particularly vulnerable to age-related loss of dopamine (DA). Therefore, the DA system is a strong candidate for therapeutic intervention to slow or reverse age related declines in cognition. In the present study, we administered a novel selective, potent, non-catechol DA D1 R agonist PF-6294 (Pfizer, Inc.) to aged female rhesus monkeys and assessed their performance on two benchmark tasks of working memory – the Delayed Non-match to Sample Task (DNMS) and Delayed Recognition Span Task (DRST). The DNMS task was administered first with the standard 10 s delay and then with 5 min delays, with and without distractors. The DRST was administered each day with four trials with unique sequences and one trial of a repeated sequence to assess evidence learning and retention. Overall, there was no significant effect of drug on performance on any aspect of the DNMS task. In contrast, we demonstrated that a middle range dose of PF-6294 significantly increased memory span on the DRST on the first and last days of testing and by the last day of testing the increased memory span was driven by the performance on the repeated trials.
format	article
author	Tara L. Moore Tara L. Moore Damon A. Young Ronald J. Killiany Ronald J. Killiany Kari R. Fonseca Dmitri Volfson David L. Gray Rita Balice-Gordon Rouba Kozak
author_facet	Tara L. Moore Tara L. Moore Damon A. Young Ronald J. Killiany Ronald J. Killiany Kari R. Fonseca Dmitri Volfson David L. Gray Rita Balice-Gordon Rouba Kozak
author_sort	Tara L. Moore
title	The Effects of a Novel Non-catechol Dopamine Partial Agonist on Working Memory in the Aged Rhesus Monkey
title_short	The Effects of a Novel Non-catechol Dopamine Partial Agonist on Working Memory in the Aged Rhesus Monkey
title_full	The Effects of a Novel Non-catechol Dopamine Partial Agonist on Working Memory in the Aged Rhesus Monkey
title_fullStr	The Effects of a Novel Non-catechol Dopamine Partial Agonist on Working Memory in the Aged Rhesus Monkey
title_full_unstemmed	The Effects of a Novel Non-catechol Dopamine Partial Agonist on Working Memory in the Aged Rhesus Monkey
title_sort	effects of a novel non-catechol dopamine partial agonist on working memory in the aged rhesus monkey
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/de9abf602a974353b8531c96d2cb9afe
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The Effects of a Novel Non-catechol Dopamine Partial Agonist on Working Memory in the Aged Rhesus Monkey

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