D1 receptors in prefrontal cells and circuits

Goldman‐Rakic, Patricia S.; Muly, E Christopher; Williams, Graham V.

doi:10.1016/s0165-0173(99)00045-4

Cited by 725 publications

(495 citation statements)

References 53 publications

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“…In the present study, the response to different doses of ITI‐214 suggests an inverted U‐shaped dose‐response, an observation also made by Snyder et al . (2016), consistent with the idea that optimal cognitive performance requires optimal engagement of prefrontal dopamine signal transduction (Goldman‐Rakic et al, 2000). Together, these data support PDE1‐linked degradation of cAMP which can be formed upon D 1 receptor activation and, thus, a potential D 1 receptor agonistic‐like effect of PDE1 inhibitors.…”

Section: Discussionsupporting

confidence: 79%

“…Indeed, immunohistochemistry suggested both a corticostriatal PDE1B expression profile in rat brains and PDE1‐D 1 receptor co‐localization in human and rat prefrontal neurons, suggesting the putative involvement of PDE1B in D 1 receptor‐dependent downstream signalling. Within the PFC, D 1 receptors have been shown to be expressed on distal dendrites and spines of pyramidal cells and GABAergic interneurons, preferentially parvalbumin‐containing basket and chandelier cells (Goldman‐Rakic et al, 2000). Given the almost complete overlap between PDE1B in D 1 receptor expression in the PFC seen in this study, the data might indicate that PDE1B is expressed by both pyramidal cells as well as interneurons.…”

Section: Discussionmentioning

confidence: 99%

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Targeting the dopamine D₁ receptor or its downstream signalling by inhibiting phosphodiesterase‐1 improves cognitive performance

Pekcec

Schülert

Stierstorfer

et al. 2018

British J Pharmacology

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Background and PurposeInsufficient prefrontal dopamine 1 (D1) receptor signalling has been linked to cognitive dysfunction in several psychiatric conditions. Because the PDE1 isoform B (PDE1B) is postulated to regulate D1 receptor‐dependent signal transduction, in this study we aimed to elucidate the role of PDE1 in cognitive processes reliant on D1 receptor function.Experimental ApproachCognitive performance of the D1 receptor agonist, SKF38393, was studied in the T‐maze continuous alternation task and 5‐choice serial reaction time task. D1 receptor/PDE1B double‐immunohistochemistry was performed using human and rat prefrontal brain sections. The pharmacological activity of the PDE1 inhibitor, ITI‐214, was assessed by measuring the increase in cAMP/cGMP in prefrontal brain tissue and its effect on working memory performance. Mechanistic studies on the modulation of prefrontal neuronal transmission by SKF38393 and ITI‐214 were performed using extracellular recordings in brain slices.Key ResultsSKF38393 improved working memory and attentional performance in rodents. D1 receptor/PDE1B co‐expression was verified in both human and rat prefrontal brain sections. The pharmacological activity of ITI‐214 on its target, PDE1, was demonstrated by its ability to increase prefrontal cAMP/cGMP. In addition, ITI‐214 improved working memory performance. Both SKF38393 and ITI‐214 facilitated neuronal transmission in prefrontal brain slices.Conclusion and ImplicationsWe hypothesize that PDE1 inhibition improves working memory performance by increasing prefrontal synaptic transmission and/or postsynaptic D1 receptor signalling, by modulating prefrontal downstream second messenger levels. These data, therefore, support the use of PDE1 inhibitors as a potential approach for the treatment of cognitive dysfunction.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Targeting the dopamine D₁ receptor or its downstream signalling by inhibiting phosphodiesterase‐1 improves cognitive performance

Pekcec

Schülert

Stierstorfer

et al. 2018

British J Pharmacology

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“…1,46 This linear relationship between the number of Met alleles and prefrontal function in healthy controls is not incompatible with an 'inverted-U' relationship between synaptic dopamine levels and prefrontal functioning, 47 assuming that under normal conditions (excluding, for example, psychostimulant administration, 48 ) Met/Met individuals have dopamine levels that are not greater than is cognitively optimal.…”

Section: Discussionmentioning

confidence: 99%

Effects of the catechol-O-methyltransferase Val158Met polymorphism on executive function: a meta-analysis of the Wisconsin Card Sort Test in schizophrenia and healthy controls

et al. 2007

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The catechol-O-methyltransferase (COMT) Val 158 Met polymorphism is hypothesized to affect executive function in patient and control populations. Studies inconsistently report better performance on the Wisconsin Card Sort Test (WCST) in individuals with one or more Met alleles. We conducted a meta-analysis of studies published until August 2006 that reported WCST perseverative errors from healthy volunteers or patients with schizophrenia-spectrum disorders. Twelve studies met inclusion criteria (total n = 1910) providing 10 samples each of patients and controls. In healthy controls, individuals with the Met/Met genotype performed better than those with the Val/Val genotype (d = 0.29; 95% confidence interval (CI) 0.02-0.55; P = 0.03), but this was not supported in the patient sample (d = À0.07; 95% CI À0.40 to 0.26; P = 0.68). Post hoc analyses suggested that Val and Met alleles are codominant in their effects on cognition. Effect size was greater in studies published at an earlier date and may also be larger in non-Caucasian samples. Gender did not affect the results. There was no evidence of publication bias. We conclude that there is small but significant relationship between Val 158 Met genotype and executive function in healthy individuals but not in schizophrenia.

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“…At the cellular level, empirical and theoretical investigations aimed at understanding how dopaminergic modulation affects the memory field and signal integration of PFC neurons have recently begun [43][44][45][46] . At a more molar level, studies are also underway that are exploring computational principles that might relate declines in neuromodulation to cognitive aging deficits observed at the information-processing and behavioral levels 12,13 .…”

Section: Neurobiological Levelmentioning

confidence: 99%

Aging cognition: from neuromodulation to representation

Lindenberger

Sikström

2001

Trends in Cognitive Sciences

816

701

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D1 receptors in prefrontal cells and circuits

Cited by 725 publications

References 53 publications

Targeting the dopamine D₁ receptor or its downstream signalling by inhibiting phosphodiesterase‐1 improves cognitive performance

Targeting the dopamine D₁ receptor or its downstream signalling by inhibiting phosphodiesterase‐1 improves cognitive performance

Effects of the catechol-O-methyltransferase Val158Met polymorphism on executive function: a meta-analysis of the Wisconsin Card Sort Test in schizophrenia and healthy controls

Aging cognition: from neuromodulation to representation

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D1 receptors in prefrontal cells and circuits

Cited by 725 publications

References 53 publications

Targeting the dopamine D1 receptor or its downstream signalling by inhibiting phosphodiesterase‐1 improves cognitive performance

Targeting the dopamine D1 receptor or its downstream signalling by inhibiting phosphodiesterase‐1 improves cognitive performance

Effects of the catechol-O-methyltransferase Val158Met polymorphism on executive function: a meta-analysis of the Wisconsin Card Sort Test in schizophrenia and healthy controls

Aging cognition: from neuromodulation to representation

Contact Info

Product

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Targeting the dopamine D₁ receptor or its downstream signalling by inhibiting phosphodiesterase‐1 improves cognitive performance

Targeting the dopamine D₁ receptor or its downstream signalling by inhibiting phosphodiesterase‐1 improves cognitive performance