Parkinson's disease: Mechanisms and models

Schultz, Wolfram. Predictive reward signal of dopamine neurons. J. Neurophysiol. 80: 1–27, 1998. The effects of lesions, receptor blocking, electrical self-stimulation, and drugs of abuse suggest t...

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Predictive Reward Signal of Dopamine Neurons

Missale, Cristina, S. Russel Nash, Susan W. Robinson, Mohamed Jaber, and Marc G. Caron. Dopamine Receptors: From Structure to Function. Physiol. Rev. 78: 189–225, 1998. — The diverse physiological actions of dopamine are mediated by at least five distinct G protein-coupled receptor subtypes. Two D1-like receptor subtypes (D1 and D5) couple to the G protein Gs and activate adenylyl cyclase. The other receptor subtypes belong to the D2-like subfamily (D2 , D3 , and D4) and are prototypic of G protein-coupled receptors that inhibit adenylyl cyclase and activate K+ channels. The genes for the D1 and D5 receptors are intronless, but pseudogenes of the D5 exist. The D2 and D3 receptors vary in certain tissues and species as a result of alternative splicing, and the human D4 receptor gene exhibits extensive polymorphic variation. In the central nervous system, dopamine receptors are widely expressed because they are involved in the control of locomotion, cognition, emotion, and affect as well as neuroendocrine s...

Dopamine Receptors: From Structure to Function

http://www.back-in-business-physiotherapy.com/images/files/DescendingControl.pdf

Descending control of pain.

http://www.columbia.edu/itc/gsas/g9600/2003/JavitchReadings/Schultz(Sulzer).pdf

Getting Formal with Dopamine and Reward

Disruption of the mouse dopamine transporter gene results in spontaneous hyperlocomotion despite major adaptive changes, such as decreases in neurotransmitter and receptor levels. In homozygote mice, dopamine persists at least 100 times longer in the extracellular space, explaining the biochemical basis of the hyperdopaminergic phenotype and demonstrating the critical role of the transporter in regulating neurotransmission. The dopamine transporter is an obligatory target of cocaine and amphetamine, as these psychostimulants have no effect on locomotor activity or dopamine release and uptake in mice lacking the transporter.

Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter

The mechanism by which psychostimulants act as calming agents in humans with attention-deficit hyperactivity disorder (ADHD) or hyperkinetic disorder is currently unknown. Mice lacking the gene encoding the plasma membrane dopamine transporter (DAT) have elevated dopaminergic tone and are hyperactive. This activity was exacerbated by exposure to a novel environment. Additionally, these mice were impaired in spatial cognitive function, and they showed a decrease in locomotion in response to psychostimulants. This paradoxical calming effect of psychostimulants depended on serotonergic neurotransmission. The parallels between the DAT knockout mice and individuals with ADHD suggest that common mechanisms may underlie some of their behaviors and responses to psychostimulants.

https://science.sciencemag.org/content/sci/283/5400/397.full.pdf

Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity.

Dopamine receptors and brain function.

The beta-adrenergic receptor kinase 1 (beta ARK1) is a member of the G protein-coupled receptor kinase (GRK) family that mediates the agonist-dependent phosphorylation and desensitization of G protein-coupled receptors. We have cloned and disrupted the beta ARK1 gene in mice by homologous recombination. No homozygote beta ARK1-/- embryos survive beyond gestational day 15.5. Prior to gestational day 15.5, beta ARK1-/- embryos display pronounced hypoplasia of the ventricular myocardium essentially identical to the "thin myocardium syndrome" observed upon gene inactivation of several transcription factors (RXR alpha, N-myc, TEF-1, WT-1). Lethality in beta ARK1-/- embryos is likely due to heart failure as they exhibit a > 70% decrease in cardiac ejection fraction determined by direct in utero intravital microscopy. These results along with the virtual absence of endogenous GRK activity in beta ARK1-/- embryos demonstrate that beta ARK1 appears to be the predominant GRK in early embryogenesis and that it plays a fundamental role in cardiac development.

https://www.pnas.org/content/pnas/93/23/12974.full.pdf

Mohamed Jaber

Papers

Dopamine Receptors: From Structure to Function

Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter

Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity.

Dopamine receptors and brain function.

Essential role of beta-adrenergic receptor kinase 1 in cardiac development and function.