Localization of dopamine D2 receptor mRNA and D1 and D2 receptor binding in the rat brain and pituitary: an in situ hybridization- receptor autoradiographic analysis

Mansour, Alfred; Meador‐Woodruff, James H.; Bunzow, James R.; Civelli, Olivier; Akil, Huda; Watson, Stanley J.

doi:10.1523/jneurosci.10-08-02587.1990

Cited by 446 publications

(274 citation statements)

References 31 publications

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“…All radiochemicals were purchased from GE Healthcare BioSciences (Piscataway, NJ). Specific binding of the dopamine D 1 -like receptor ligand [ 3 H]SCH233090 (1 nM) to the brain slice was analyzed by autoradiography as described (Mansour et al, 1990). The brain slices were pre-incubated for 15 min in 50 mM Tris-HCl buffer (pH 7.4, 251C) containing 120 mM NaCl, 5 mM KCl, and 1 mM MgCl 2 .…”

Section: Autoradiographymentioning

confidence: 99%

Chronic Fluoxetine Selectively Upregulates Dopamine D1-Like Receptors in the Hippocampus

Kobayashi

Haneda

Higuchi³

et al. 2012

Neuropsychopharmacol

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The dentate gyrus of the hippocampus has been implicated in mechanisms of action of selective serotonin reuptake inhibitors (SSRIs). We have recently demonstrated that the SSRI fluoxetine can reverse the state of maturation of the adult dentate granule cells and enhances serotonin 5-HT 4 receptor-mediated synaptic potentiation at the synapses formed by their mossy fiber axons. Here, we show that fluoxetine can induce long-lasting enhancement of dopaminergic modulation at the mossy fiber synapse. Synaptic responses arising from the mossy fiber-CA3 pyramidal cell synapse were recorded using acute mouse hippocampal slices. Dopamine potentiates mossy fiber synaptic transmission by activating D 1 -like receptors. Chronic fluoxetine treatment induced a prominent increase in the magnitude of dopamine-induced synaptic potentiation, and this effect was maintained at least up to 1 month after withdrawal of fluoxetine. Quantitative autoradiography revealed that binding of the D 1 -like receptor ligand [ 3 H]SCH23390 was selectively increased in the dentate gyrus and along the mossy fiber in fluoxetine-treated mice. However, binding of the 5-HT 4 receptor ligand [ 3 H]GR113808 was not significantly changed. These results suggest that chronic fluoxetine enhanced the dopaminergic modulation at least in part by upregulating expression of D 1 -like receptors, while the enhanced serotonergic modulation may be mediated by modifications of downstream signaling pathways. These enhanced monoaminergic modulations would greatly increase excitatory drive to the hippocampal circuit through the dentate gyrus. The highly localized upregulation of D 1 -like receptors further supports the importance of the dentate gyrus in the mechanism of action of SSRIs.

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Section: Autoradiographymentioning

confidence: 99%

Chronic Fluoxetine Selectively Upregulates Dopamine D1-Like Receptors in the Hippocampus

Kobayashi

Haneda

Higuchi³

et al. 2012

Neuropsychopharmacol

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“…Discrepancies between mRNA and protein levels are not uncommon (Mansour et al, 1990(Mansour et al, , 1991 and may be due to a number of different factors. For example, D2 receptor mRNA is localized primarily in the cell bodies of prefrontal neurons, but D2 receptor protein is present in both presynaptic and postsynaptic elements, and therefore the population of neurons sampled by the two measures may be quite different.…”

Section: Effects Of Past Experience With Self-administered Cocaine Onmentioning

confidence: 99%

Persistent Alterations in Cognitive Function and Prefrontal Dopamine D2 Receptors Following Extended, but Not Limited, Access to Self-Administered Cocaine

Briand

Flagel²,

García-Fuster³

et al. 2008

Neuropsychopharmacol

123

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Drug addicts have deficits in frontocortical function and cognition even long after the discontinuation of drug use. It is not clear, however, whether the cognitive deficits are a consequence of drug use, or are present prior to drug use, and thus are a potential predisposing factor for addiction. To determine if self-administration of cocaine is capable of producing long-lasting alterations in cognition, rats were allowed access to cocaine for either 1 h/day (short access, ShA) or 6 h/day (long access, LgA) for 3 weeks. Between 1 and 30 days after the last self-administration session, we examined performance on a cognitively demanding test of sustained attention that requires an intact medial prefrontal cortex. The expression levels of dopamine D1 and D2 receptor mRNA and D2 protein in the prefrontal cortex were also examined. Early after discontinuation of drug use, LgA (but not ShA) animals were markedly impaired on the sustained attention task. Although the LgA animals improved over time, they continued to show a persistent pattern of performance deficits indicative of a disruption of cognitive flexibility up to 30 days after the discontinuation of drug use. This was accompanied by a significant decrease in DA D2 (but not D1) mRNA in the medial and orbital prefrontal cortex, and D2 receptor protein in the medial prefrontal cortex of LgA (but not ShA) animals. These findings establish that repeated cocaine use is capable of producing persistent alterations in the prefrontal cortex and in cognitive function, and illustrate the usefulness of extended access self-administration procedures for studying the neurobiology of addiction.

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“…Dopamine-D2 receptors in the brain are strongly expressed in post-synaptic regions such as cortex, striatum, and nucleus accumbens in addition to pre-synaptic dopaminergic neurons of the substantia nigra and ventral tegmental area (37). Freud-1 is also expressed in pre-synaptic dopaminergic cells of the substantia nigra (10) and in embryonic and post-natal striatum and cortex, which express dopamine-D2 receptors (12).…”

Section: Freud-1 Mediated Repression Of the Dopamine-d2mentioning

confidence: 99%

Differential Repression by Freud-1/CC2D1A at a Polymorphic Site in the Dopamine-D2 Receptor Gene

Rogaeva

Jafar‐Nejad

et al. 2007

Journal of Biological Chemistry

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Freud-1/CC2D1A is a transcriptional repressor of the serotonin-1A receptor gene and was recently genetically linked to non-syndromic mental retardation. To identify new Freud-1 gene targets, data base mining for Freud-1 recognition sequences was done. A highly homologous intronic element (D2-DRE) was identified in the human dopamine-D2 receptor (DRD2) gene, and the role of Freud-1 in regulating the gene at this site was assessed. Recombinant Freud-1 bound specifically to the D2-DRE, and a major protein-D2-DRE complex was identified in nuclear extracts that was supershifted using Freud-1-specific antibodies. Endogenous Freud-1 binding to the D2-DRE in cells was detected using chromatin immunoprecipitation. The D2-DRE conferred strong repressor activity in transcriptional reporter assays that was dependent on the Freud-1 recognition sequence. In three different human cell lines, the level of Freud-1 protein was inversely related to DRD2 expression. Knockdown of endogenous Freud-1 using small interfering RNA resulted in an up-regulation of DRD2 RNA and binding sites, demonstrating a crucial role for Freud-1 in DRD2 regulation. A previously uncharacterized single nucleotide A/G polymorphism (rs2734836) was located adjacent to the D2-DRE and conferred allele-specific Freud-1 binding and repression, with the major G-allele having reduced activity. These studies demonstrate a key role for Freud-1 to regulate DRD2 expression and provide the first mechanistic insights into its transcriptional regulation. Allele-specific regulation of DRD2 expression by Freud-1 may possibly associate with psychiatric disorders or mental retardation.Dopamine-D2 receptors function as both pre-synaptic autoreceptors and post-synaptic receptors, and play key roles in regulating dopaminergic neurotransmission. Increased levels of dopamine-D2 receptors or dopaminergic hyperactivity have been implicated in schizophrenia (1-3), and most antipsychotic drugs inhibit dopamine-D2 receptors (4 -6). Although transcriptional regulation of the rat dopamine D2 receptor (DRD2) 5 gene has been examined, very little is known regarding the regulation of the human DRD2 gene. A polymorphism in the putative DRD2 promoter confers decreased transcriptional activity and has been negatively associated with schizophrenia (7). However, the transcriptional mechanisms for regulation of the human DRD2 gene have yet to be elucidated.To identify new transcriptional regulators in the nervous system, we previously characterized the serotonin-1A (5-HT1A) receptor promoter region and identified a novel dual repressor element (DRE) that negatively regulates its expression (8, 9). The DRE consists of adjacent and partially overlapping repressor elements: 5Ј-repressor element (FRE; major regulator in neuronal cells) and 3Ј-repressor element (9). Analysis of DREbinding proteins revealed that a novel protein, Freud-1 (Five prime repressor under dual repression-binding protein-1)/ CC2D1A (Coiled-coil and C2 Domain containing 1A) binds to and represses the 5-HT1A receptor gene throug...

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Localization of dopamine D2 receptor mRNA and D1 and D2 receptor binding in the rat brain and pituitary: an in situ hybridization- receptor autoradiographic analysis

Cited by 446 publications

References 31 publications

Chronic Fluoxetine Selectively Upregulates Dopamine D1-Like Receptors in the Hippocampus

Chronic Fluoxetine Selectively Upregulates Dopamine D1-Like Receptors in the Hippocampus

Persistent Alterations in Cognitive Function and Prefrontal Dopamine D2 Receptors Following Extended, but Not Limited, Access to Self-Administered Cocaine

Differential Repression by Freud-1/CC2D1A at a Polymorphic Site in the Dopamine-D2 Receptor Gene

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