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Dopamine's Actions in Primate Prefrontal Cortex: Challenges for Treating Cognitive Disorders.
Amy F T Arnsten1, Min Wang2, Constantinos D Paspalas2
1Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut amy.arnsten@yale.edu.
Pharmacological Reviews
|June 25, 2015
Summary
Dopamine (DA) influences prefrontal cortex (PFC) working memory via D1 and D2 receptors. Optimal D1 receptor stimulation enhances cognition, while dysregulation is linked to schizophrenia.
Area of Science:
- Neuroscience
- Cognitive Science
Background:
- The prefrontal cortex (PFC) and cortical dopamine (DA) show parallel elaboration in primates.
- Dopaminergic cells signaling salient events project to the dorsolateral PFC (dlPFC).
- Dopamine's essential role in dlPFC working memory has been recognized since 1979.
Purpose of the Study:
- To explore the differential roles of D1 and D2 receptors in PFC function.
- To understand how dopamine receptor subtypes modulate working memory and neuronal firing.
- To identify potential therapeutic targets for cognitive deficits associated with D1 receptor dysregulation.
Main Methods:
- Review of existing literature on dopamine receptor function in the PFC.
- Analysis of D1 and D2 receptor localization and effects on neuronal activity.
- Discussion of implications for cognitive disorders like schizophrenia.
Main Results:
- D1 receptor stimulation exhibits an inverted U-shaped effect on visuospatial working memory and delay cell firing, with optimal levels enhancing performance and higher levels impairing it.
- D2 receptor stimulation influences response cells, potentially relating to positive symptoms in schizophrenia.
- Dopamine's effects may extend to ventrolateral PFC and frontal eye fields, with orbital PFC research being a nascent area.
Conclusions:
- Dopamine receptor subtypes differentially regulate PFC functions, impacting working memory and neuronal representations.
- Dysregulation of D1 receptors is implicated in cognitive deficits, suggesting a need for novel agonists.
- Further research into PFC dopamine signaling, particularly in the orbital PFC, holds promise for understanding and treating cognitive disorders.
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