Molecular biology of dopamine receptors

Sibley, David R.; Monsma, Frederick J.

doi:10.1016/0165-6147(92)90025-2

Cited by 904 publications

(551 citation statements)

References 30 publications

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“…* These authors contributed equally to this work. D3R and D4R, respectively) [47]. Although signaling via the adenylyl cyclase-cAMP system is the principal mode of action, dopamine receptors also activate phospho-lipase C via the Gq/ 11 system and increase intracellular calcium levels [16,39].…”

Section: Introductionmentioning

confidence: 99%

Dopamine receptor mRNA and protein expression in the mouse corpus striatum and cerebral cortex during pre- and postnatal development

2007

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The outcome of dopaminergic signaling and effectiveness of dopaminergic drugs depend on the relative preponderance of each of the five dopamine receptors in a given brain region. The separate contribution of each receptor to overall dopaminergic tone is difficult to establish at a functional level due to lack of receptor subtype specific pharmacological agents. A surrogate for receptor function is receptor protein or mRNA expression. We examined dopamine receptor mRNA expression by quantitative reverse transcription real-time PCR in the striatum, globus pallidus, frontal cortex and cingulate cortex of embryonic and postnatal mice. Samples of each region were collected by laser capture microdissection. D1-and D2-receptor mRNAs were the most abundant in all the regions of the mature brain. The D1-receptor was predominant over the D2-receptor in the frontal and cingulate cortices whereas the situation was reversed in the striatum and globus pallidus. In the proliferative domains of the embryonic forebrain, D3-, D4-and D5-receptors were predominant. In the corpus striatum and cerebral cortex, the D3-and D4-receptors were the only receptors that showed marked developmental regulation. By analyzing D1 receptor protein expression, we show that developmental changes in mRNA expression reliably translate into changes in protein levels, at least for the D1-receptor.

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Section: Introductionmentioning

confidence: 99%

Dopamine receptor mRNA and protein expression in the mouse corpus striatum and cerebral cortex during pre- and postnatal development

2007

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“…However, at the cellular level, D 1 [79,80]). Therefore, it is important to distinguish between the specific contributions of D 1 and D 2 activity in the MPOA to male copulatory behavior.…”

Section: Microinjection Of Dopamine Agonistsmentioning

confidence: 99%

Dopamine, the medial preoptic area, and male sexual behavior

Domínguez

Hull

2005

Physiology & Behavior

247

190

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“…There are two classes of dopamine receptors, the D 1 and the D 2 . The D 1 class includes both D 1 and D 5 receptors, while the D 2 class includes D 2 , D 3 , and D 4 receptors (Sibley and Monsma, 1992). In terms of this discussion, we will focus on D 1 and D 2 receptors in view of their high density in the striatum and their relevance to the pharmacology of cocaine.…”

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confidence: 99%

D₁ dopamine receptor: A putative neurochemical and behavioral link to cocaine action

Hummel

Unterwald

2002

Journal Cellular Physiology

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Cocaine is one of the most abused psychostimulants known to man and as such, researchers have been steadfast in their attempts to understand the neurobiological mechanisms responsible for its abuse. Cocaine undoubtedly wreaks havoc on a number of mammalian neuronal neurotransmitter systems, and it is maintained that this dysregulatory effect supports cocaine abuse. Cocaine's mechanism of action has been well described. Cocaine binds differentially to the dopamine, serotonin, and norepinephrine transport proteins and directly prevents the reuptake of dopamine, serotonin, and norepinephrine into pre-synaptic neurons (Heikkila et al., 1975, Biochem Pharmacol 24(8):847±852;Reith et al., 1986, Biochem Pharmacol 35(7):1123±1129; Ritz et al., 1987, Science 237:1219± 1223. Inhibition of re-uptake subsequently elevates the synaptic concentrations of each of these neurotransmitters. In addition to this direct effect, cocaine also produces a number of indirect actions, which alter other neuromodulatory systems (i.e., opioidergic, glutamatergic, and GABAergic systems). Many of these effects are just beginning to be elucidated, but nonetheless contribute to this agent's diverse pharmacological pro®le. Interestingly, it is the indirect actions of this melli¯uous molecule, which mediate most of its sought and unsought effects. The intricacy with which cocaine produces neuronal alterations beyond its direct effects on neurotransmitter re-uptake appear to be most relevant to cocaine abuse, and hence the phenomenon of addiction. In light of cocaine's multifarious effects on numerous neuronal systems, its effect on dopaminergic neurotransmission has attracted the most attention, particularly because of the implicated role of dopamine in brain reward. Pharmacologically, the psychostimulant effects of cocaine appear to be mediated by its ability to enhance dopaminergic activity within the mesocorticolimbic circuit (Roberts et al., 1977, Pharmacol Biochem Behav 6(6):615±620). Additionally, it is the intensity with which cocaine produces alterations in dopaminergic circuitry that have enabled this drug to prevail as one of the most addictive substances known to man. This review will summarize ®ndings relevant to cocaine-induced alterations in dopaminemediated signal transduction. Speci®cally, it will concentrate on the D 1 dopamine receptor and intracellular signaling mediated by this receptor subtype. It will describe cocaine-induced cellular and behavioral alterations relevant to this pathway and how these changes potentially effect gene transcription and protein expression. This article too will review a common behavioral manifestation associated with repeated cocaine exposure, sensitization, and why the D 1 dopamine receptor and its associated signaling pathway have been implicated in this phenomenon. Lastly, this article will discuss how targeting the D 1 dopamine receptor and its signaling pathway may offer some insight into understanding cocaine addiction, a somewhat elusive brain disease.

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Molecular biology of dopamine receptors

Cited by 904 publications

References 30 publications

Dopamine receptor mRNA and protein expression in the mouse corpus striatum and cerebral cortex during pre- and postnatal development

Dopamine receptor mRNA and protein expression in the mouse corpus striatum and cerebral cortex during pre- and postnatal development

Dopamine, the medial preoptic area, and male sexual behavior

D₁ dopamine receptor: A putative neurochemical and behavioral link to cocaine action

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Molecular biology of dopamine receptors

Cited by 904 publications

References 30 publications

Dopamine receptor mRNA and protein expression in the mouse corpus striatum and cerebral cortex during pre- and postnatal development

Dopamine receptor mRNA and protein expression in the mouse corpus striatum and cerebral cortex during pre- and postnatal development

Dopamine, the medial preoptic area, and male sexual behavior

D1 dopamine receptor: A putative neurochemical and behavioral link to cocaine action

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Product

Resources

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D₁ dopamine receptor: A putative neurochemical and behavioral link to cocaine action