D2-like dopamine receptors are thought to control presynaptic dopamine synthesis and release. Because these receptors comprise a family which includes D2, D3 and D4 dopamine receptors, the question arises as to which subtype performs what role(s). To investigate the potential autoreceptor roles of these proteins, D2, D3 and D4 receptors were transfected into a mesencephalic clonal cell line which synthesizes and releases dopamine. Here we report that stimulation of transfected D2 and D3 receptors, but not D4 receptors, inhibits dopamine release from this dopaminergic cell line. This is the first report of a functional role for D3 receptors and establishes these cell lines as a convenient in vitro model system to study signal transduction mechanisms associated with autoreceptor function.
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Annu Rev Pharmacol Toxicol
January 2025
Department of Pharmacology and Toxicology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; email:
G protein-coupled receptors (GPCRs) represent the largest family of plasma membrane proteins targeted for therapeutic development. For decades, GPCRs were investigated as monomeric entities during analysis of their pharmacology or signaling and during drug development. However, a considerable body of evidence now indicates that GPCRs function as dimers or higher-order oligomers.
View Article and Find Full Text PDFFront Neurosci
January 2025
The Key Laboratory of Anesthesia and Organ Protection, The Key Laboratory of Brain Science, Zunyi Medical University, Zunyi, China.
Background: The ventrolateral preoptic nucleus (VLPO) is a crucial regulator of sleep, and its neurons are implicated in both sleep-wake regulation and anesthesia-induced loss of consciousness. Propofol (PRO), a widely used intravenous anesthetic, modulates the activity of VLPO neurons, but the underlying mechanisms, particularly the role of dopaminergic receptors, remain unclear.
Objective: This study aimed to investigate the effects of PRO on NA (-) neurons in the VLPO and to determine the involvement of D1 and D2 dopaminergic receptors in mediating these effects.
Curr Gene Ther
January 2025
Department of Pharmacology, Delhi Pharmaceutical Sciences & Research University, Delhi, 110017, India.
The dopamine (DA) system is central to mood regulation, motivation, and reward processing, making it a critical focus for understanding Major Depressive Disorder (MDD). While the dopaminergic system's role in MDD pathophysiology has been acknowledged, gaps remain in linking specific receptor subtypes and genetic factors to depression-like phenotypes. This study explores the interplay between dopamine receptor subtypes (D1-D5) and associated genetic variations, particularly focusing on receptor heterodimers and polymorphisms influencing dopamine biosynthesis, signalling, and metabolism.
View Article and Find Full Text PDFElife
January 2025
Max Planck Institute for Metabolism Research, Department of Neuronal Control of Metabolism, Cologne, Germany.
Orexin signaling in the ventral tegmental area and substantia nigra promotes locomotion and reward processing, but it is not clear whether dopaminergic neurons directly mediate these effects. We show that dopaminergic neurons in these areas mainly express orexin receptor subtype 1 (Ox1R). In contrast, only a minor population in the medial ventral tegmental area express orexin receptor subtype 2 (Ox2R).
View Article and Find Full Text PDFJ Neurosci
January 2025
Laboratory on Neurobiology of Compulsive Behaviors, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, 20892. USA.
Dopamine critically regulates neuronal excitability and promotes synaptic plasticity in the striatum, thereby shaping network connectivity and influencing behavior. These functions establish dopamine as a key neuromodulator, whose release properties have been well-studied in rodents but remain understudied in nonhuman primates. This study aims to close this gap by investigating the properties of dopamine release in macaque striatum and comparing/contrasting them to better-characterized mouse striatum, using ex vivo brain slices from male and female animals.
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