Distribution of D4 dopamine receptor in rat brain with sequence-specific antibodies

Defagot, María Cristina; Malchiodi, Emilio L.; Villar, Marcelo J.; Antonelli, Marta C.

doi:10.1016/s0169-328x(96)00235-5

Cited by 137 publications

(90 citation statements)

References 30 publications

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“…These findings, combined with the observations of high levels of DRD4 expression in PFC (Ariano et al, 1997;Defagot et al, 1997;Matsumoto et al, 1995) raise a possibility of C allele dose-dependent PFC responses during perceptual novelty encoding. Contrary to prediction, this genotype-dependent effect was not observed, nor do we observe adaptation of prefrontal responses with repeated oddball presentation, which has been described previously (Yamaguchi et al, 2004).…”

Section: Responses In the Prefrontal Cortexmentioning

confidence: 70%

“…Drd4 gene knockout mice show decreased exploration in response to novel stimuli (Dulawa et al, 1999;Rubinstein et al, 1997), whereas a selective D4 receptor agonist increases novel object exploration in mice (Powell et al, 2003). The D4 receptor is preferentially expressed in limbic regions, including the hippocampus (Mrzljak et al, 1996), prefrontal cortex (Ariano et al, 1997;Defagot et al, 1997;Matsumoto et al, 1995), and globus pallidus (Mrzljak et al, 1996). Although D4 receptor expression has been shown in primate SN, this is in SN pars reticulata (Mrzljak et al, 1996) and not the SN pars compacta or VTA which contain the majority of dopaminergic neurones in the SN/VTA (Duzel et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…Although D4 receptor expression has been shown in primate SN, this is in SN pars reticulata (Mrzljak et al, 1996) and not the SN pars compacta or VTA which contain the majority of dopaminergic neurones in the SN/VTA (Duzel et al, 2009). D4 receptor expression in SN pars compacta has, however, been shown in rodents (Defagot et al, 1997). In humans, the rather small (3.5 kb) DRD4 gene has generated much interest due to a high degree of functional variability, and an observed association between functional DRD4 polymorphisms and attention deficit/hyperactivity disorder (ADHD) (Franke et al, 2011), substance abuse (Li et al, 2011) and the personality trait of novelty seeking (NS) (Munafo et al, 2008b), which is considered a characteristic feature of both disorders.…”

Section: Introductionmentioning

confidence: 99%

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Dopamine receptor 4 promoter polymorphism modulates memory and neuronal responses to salience

et al. 2014

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Animal models and human functional imaging data implicate the dopamine system in mediating enhanced encoding of novel stimuli into human memory. A separate line of investigation suggests an association between a functional polymorphism in the promoter region for the human dopamine 4 receptor gene (DRD4) and sensitivity to novelty. We demonstrate, in two independent samples, that the -5210T DRD4 promoter polymorphism determines the magnitude of human memory enhancement for contextually novel, perceptual oddball stimuli in an allele dose-dependent manner. The genotype-dependent memory enhancement conferred by the C allele is associated with increased neuronal responses during successful encoding of perceptual oddballs in the ventral striatum, an effect which is again allele dose-dependent. Furthermore, with repeated presentations of oddball stimuli, this memory advantage decreases, an effect mirrored by adaptation of activation in the hippocampus and substantia nigra/ventral tegmental area in C carriers only. Thus, a dynamic modulation of human memory enhancement for perceptually salient stimuli is associated with activation of a dopaminergic-hippocampal system, which is critically dependent on a functional polymorphism in the DRD4 promoter region.

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Section: Responses In the Prefrontal Cortexmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dopamine receptor 4 promoter polymorphism modulates memory and neuronal responses to salience

et al. 2014

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“…57 Another immunocytochemical study using different D 4 antibodies generated against a selective segment from the third intracellular loop of rat D 4 receptor indicated a wider distribution of D 4 receptors in rat brain, including substantial levels in CPu and NAc. 58 Such differences in D 4 receptor localization may stem from differences in the specific epitopic peptide sequences used to generate antibodies against D 4 receptor protein.…”

Section: Radioligand Assaysmentioning

confidence: 99%

Dopamine D4 receptors: significance for molecular psychiatry at the millennium

Tarazi

Baldessarini

1999

Mol Psychiatry

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Cloning of dopamine D 4 receptor genesThe human D 4 receptor gene (D4DR) was initially cloned from human neuroblastoma cells using probes complementary to mRNA sequences required to synthesize D 2 receptor proteins, and was found to encode a protein product typically containing 387 amino acids. 3 The D4DR gene was soon localized to region 15.5 of the long (q) arm of human chromosome 11. 4 with an initial external amino terminus and final intracellular segment ending with a carboxy moiety. The third intracellular cytoplasmic loop (IL 3 ) of the receptor peptide chain between the proposed fifth and sixth transmembrane segments (TM V , TM VI ) and the intracytoplasmic carboxyl terminal segment are believed to couple to G-proteins and interact with other molecular elements involved in DA-mediated synaptic neurotransmission. 3 Indeed, the molecular differentiation of the five main members of the DA receptor family is based largely on the length and amino acid sequences of IL 3 and the intracellular carboxy terminal segment. 1 The D 4 receptor protein contains several post-translationally modifiable elements common to D 2 -like DA receptors, including at least one potential site for Nlinked glycosylation in the extracellular amino terminus, several likely phosphorylation sites in IL 3 that may act as targets for protein kinases A and C, a cysteine residue at the end of the carboxyl terminal segment, two serine residues in the third cytoplasmic domain that may provide positive charge involving in 'docking' of the electronegative catechol groups of DA, and two acidic aspartate residues within TM II and TM III that may account for docking of the amino group of DA. 1,3 Additional features include disulfide bridging of TM III and TM IV that may contribute to the stability of a proposed cup-like arrangement of the D 4 receptor protein in the lipid membrane environment. 5 The D 4 receptor peptide sequence also contains several putative domains (the Src homology 3 [SH3] binding regions that strongly interact with small adapter peptides, including Grb2 and Nck, required for full func-

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“…Most immunohistochemical studies of D2-like receptors so far have used only a single antibody, with the notable exception of two studies of DRD4 that used antibodies against two epitopes (Defagot et al 1997; Mauger et al 1998). Use of antibodies against two or more epitopes is the best safeguard against cross-reaction, especially with monoclonal antibodies (Morris 1998).…”

Section: Introductionmentioning

confidence: 99%

Endosomal location of dopamine receptors in neuronal cell cytoplasm

Wolstencroft

Šimić²,

Mân

et al. 2007

J Mol Hist

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Five subtypes of dopamine receptor exist in two subfamilies: two D1-like (D1 and D5) and three D2-like (D2, D3 and D4). We produced novel monoclonal antibodies against all three D2-like receptors and used them to localize receptors in Ntera-2 (NT-2) cells, the human neuronal precursor cell line. Most of the immunostaining for all three receptors colocalized with mannose-6-phosphate receptor, a marker for late endosomes formed by internalization of the plasma membrane. This result was obtained with antibodies against three different epitopes on the D3 receptor, to rule out the possibility of cross-reaction with another protein, and controls without primary antibody or in the presence of competitor antigen were completely negative. In rat cerebral cortex and hippocampus, some of the dopamine receptor staining was found in similar structures in neuronal cell cytoplasm. Only some of the neurons were positive for dopamine receptors and the pattern was consistent with previously-reported patterns of innervation by dopamine-producing neurons. Endosomal dopamine receptors may provide a useful method for identifying cell bodies of dopamine-responsive neurons to complement methods that detect only active receptors in the neuronal cell membrane.

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Distribution of D4 dopamine receptor in rat brain with sequence-specific antibodies

Cited by 137 publications

References 30 publications

Dopamine receptor 4 promoter polymorphism modulates memory and neuronal responses to salience

Dopamine receptor 4 promoter polymorphism modulates memory and neuronal responses to salience

Dopamine D4 receptors: significance for molecular psychiatry at the millennium

Endosomal location of dopamine receptors in neuronal cell cytoplasm

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