Author
Mohamed Jaber
Other affiliations: Howard Hughes Medical Institute, Duke University
Bio: Mohamed Jaber is an academic researcher from University of Bordeaux. The author has contributed to research in topics: Dopamine & Dopaminergic. The author has an hindex of 18, co-authored 23 publications receiving 8659 citations. Previous affiliations of Mohamed Jaber include Howard Hughes Medical Institute & Duke University.
Papers
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TL;DR: Target deletion of several of these dopamine receptor genes in mice should provide valuable information about their physiological functions and provide unequivocal evidence for the involvement of one of these receptors in the etiology of various central nervous system disorders.
Abstract: 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...
3,433 citations
TL;DR: 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.
Abstract: 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.
2,439 citations
TL;DR: 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.
Abstract: 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.
847 citations
TL;DR: The recent characterization of D3 and D4 receptors which are, interestingly, expressed in areas of the CNS mediating cognition and affect or showing increased affinity for certain neuroleptics, have renewed the interest and hope of finding effective neurolePTics devoid of side effects.
565 citations
TL;DR: It is demonstrated that beta ARK1 appears to be the predominant GRK in early embryogenesis and that it plays a fundamental role in cardiac development.
Abstract: 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.
339 citations
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TL;DR: PD models based on the manipulation of PD genes should prove valuable in elucidating important aspects of the disease, such as selective vulnerability of substantia nigra dopaminergic neurons to the degenerative process.
4,872 citations
TL;DR: Dopamine systems may have two functions, the phasic transmission of reward information and the tonic enabling of postsynaptic neurons.
Abstract: 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...
3,962 citations
TL;DR: Target deletion of several of these dopamine receptor genes in mice should provide valuable information about their physiological functions and provide unequivocal evidence for the involvement of one of these receptors in the etiology of various central nervous system disorders.
Abstract: 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...
3,433 citations
TL;DR: The present review focuses on the organisation of descending pathways and their pathophysiological significance, the role of individual transmitters and specific receptor types in the modulation and expression of mechanisms of descending inhibition and facilitation and the advantages and limitations of established and innovative analgesic strategies which act by manipulation of descending controls.
2,565 citations
TL;DR: Recent neurophysiological studies reveal that neurons in certain brain structures carry specific signals about past and future rewards, and the optimal use of rewards in voluntary behavior would benefit from interactions between the signals.
2,478 citations