The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Pierre Sokoloff - One of the best experts on this subject based on the ideXlab platform.
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interactions of gipc with dopamine d2 d3 but not d4 receptors define a novel mode of regulation of g protein coupled receptors
2003Co-Authors: Freddy Jeanneteau, Pierre Sokoloff, Jorge Diaz, Nathalie GriffonAbstract:The C-terminus domain of G protein-coupled receptors confers a functional cytoplasmic interface involved in protein association. By screening a rat brain cDNA library using the yeast two-hybrid system with the C-terminus domain of the dopamine D3 receptor (D3R) as bait, we characterized a new interaction with the PDZ domain-containing protein, GIPC (GAIP interacting protein, C terminus). This interaction was specific for the dopamine D2 receptor (D2R) and D3R, but not for the dopamine D4 receptor (D4R) subtype. Pull-down and affinity chromatography assays confirmed this interaction with recombinant and endogenous proteins. Both GIPC mRNA and protein are widely expressed in rat brain and together with the D3R in neurons of the Islands of Calleja at plasma membranes and in vesicles. GIPC reduced D3R signaling, cointernalized with D2R and D3R, and sequestered receptors in sorting vesicles to prevent their lysosomal degradation. Through its dimerization, GIPC acts as a selective scaffold protein to assist receptor functions. Our results suggest a novel function for GIPC in the maintenance, trafficking, and signaling of GPCRs.
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Interactions of GIPC with Dopamine D 2,D 3 but not D 4 Receptors Define a Novel Mode of Regulation of G Protein–coupled Receptors
2003Co-Authors: Freddy Jeanneteau, Pierre Sokoloff, Jorge Diaz, Nathalie Griffon, Suzanne PfefferAbstract:The C-terminus domain of G protein–coupled receptors confers a functional cytoplasmic interface involved in protein association. By screening a rat brain cDNA library using the yeast two-hybrid system with the C-terminus domain of the dopamine D 3 receptor (D 3R) as bait, we characterized a new interaction with the PDZ domain-containing protein, GIPC (GAIP interacting protein, C terminus). This interaction was specific for the dopamine D 2 receptor (D 2R) and D 3R, but not for the dopamine D 4 receptor (D 4R) subtype. Pull-down and affinity chromatography assays confirmed this interaction with recombinant and endogenous proteins. Both GIPC mRNA and protein are widely expressed in rat brain and together with the D 3R in neurons of the Islands of Calleja at plasma membranes and in vesicles. GIPC reduced D 3R signaling, cointernalized with D 2R and D 3R, and sequestered receptors in sorting vesicles to prevent their lysosomal degradation. Through its dimerization, GIPC acts as a selective scaffold protein to assist receptor functions. Our results suggest a novel function for GIPC in the maintenance, trafficking, and signaling of GPCRs
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coexpression of dopamine d1 and d3 receptors in Islands of Calleja and shell of nucleus accumbens of the rat opposite and synergistic functional interactions
1998Co-Authors: Sophie Ridray, Jeancharles Schwartz, Nathalie Griffon, Virginie Mignon, Evelyne Souil, Suzanna Carboni, Jorge Soler A Diaz, Pierre SokoloffAbstract:Using double in situ hybridization, we found extensive coexpression of dopamine D1 and D3 receptor (D1R and D3R) mRNAs in neurons of the island of Calleja major (ICjM) and ventromedial shell of nucleus accumbens (ShV), respectively. Thus, at least 79 and 63% of D3R mRNA-expressing neurons in ICjM and ShV also expressed the D1R mRNA. Coexpression of D1R and D3R mRNAs was found to occur in substance P (SP) mRNA-expressing neurons in both areas, suggesting SP mRNA as a marker of the activity of coexpressing neurons. Administration of SKF 38393, a D1R receptor agonist, increased c-fos mRNA in ICjM, whereas administration of quinpirole, a D2R/D3R agonist, decreased it; SCH 23390, a D1R antagonist and nafadotride, a preferential D3R antagonist, given alone, had effects opposite to those of the corresponding agonists. These data indicate that basal c-fos expression in ICjM is maintained by endogenous dopamine acting tonically upon two receptor subtypes subserving opposite effects on the same cell. However, in ShV, whereas SKF 38393 also increased c-fos mRNA, quinpirole had no effect, a difference presumably reflecting the lower fraction of neurons coexpressing D1R and D3R in this area. In contrast, in ShV from reserpine-treated rats, SKF 38393 increased SP mRNA and quinpirole potentiated this effect. These contrasting interactions of D1R- and D3R-mediated signalling events, i.e. in either opposite or synergistic directions, most likely occurring at the single cell level, may serve to increase the dopamine response threshold of the target cells in ICjM and to maintain a strong tonic activity of ShV neurons.
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d3 dopamine receptor mrna is widely expressed in the human brain
1998Co-Authors: Michio Suzuki, Yasmin L. Hurd, Pierre Sokoloff, Jeancharles Schwartz, Goran SedvallAbstract:Abstract Considerable attention has been given to the association of the D3 dopamine receptor subtype and limbic function based on the abundant localization of D3 receptor sites and mRNA expression in the Islands of Calleja and nucleus accumbens in experimental animals. Though most human anatomical studies have focused on the role of D3 receptors in limited brain structures, detailed information about the overall anatomical organization of the D3 receptor in the human brain is still, however, not available. In the current study, we examined the anatomical distribution of D3 receptor mRNA expression at different levels of the human brain in whole hemisphere horizontal cryosections using in situ hybridization. This approach made it possible to establish for the first time the wide and heterogenous expression of the D3 receptor gene throughout the human brain. As expected, the most abundant D3 mRNA expression levels were found in the Islands of Calleja and discrete cell cluster populations within the ventral striatum/nucleus accumbens region. High levels were also evident within the dentate gyrus and striate cortex. Low to moderate D3 mRNA expression levels were apparent in most brain areas including all other cortical regions (highest in the anterior cingulate/subcallosal gyrus), caudate nucleus, putamen, anterior and medial thalamic nucleus, mammillary body, amygdala, hippocampal CA region, lateral geniculate body, substantia nigra pars compacta, locus coeruleus, and raphe nuclei. While the current anatomical map of D3 receptor mRNA expression in the human brain does confirm previous reports that D3 receptors may play important roles in limbic-related functions such as emotion and cognition, the findings also suggest other non-limbic functions for D3 mRNA-expressing cell populations such as processing of motor and sensory information.
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phenotypical characterization of neurons expressing the dopamine d3 receptor in the rat brain
1995Co-Authors: Jorge Diaz, Nathalie Griffon, D Levesque, C H Lammers, Mariepascale Martres, J C Schwartz, Pierre SokoloffAbstract:Abstract We have established the cellular distribution of the dopamine D3 receptor using tritiated 7-hydroxy-N-N-di-n-propyl-2-aminotetralin and a complementary RNA probe to visualize autoradiographically the protein in binding studies and the gene transcripts byin situ hybridization, respectively. Studies with these two markers confirm the restricted expression of the D3 receptor in few brain areas, i.e. mainly the ventral striatal complex, the substantia nigra-ventral tegmental area and the cerebellum. In nucleus accumbens, the D3 receptor was mainly expressed in medium-sized neurons of the rostral pole and ventromedial shell subdivisions, but not of the core or septal pole, i.e. accumbal subdivisions expressing the D2 receptor. In the ventromedial shell, about 60% of the D3 receptor-expressing neurons were neurotensin neurons, presumably projecting to the ventral pallidum. In the Islands of Calleja, both D3 receptor binding and messenger RNA were abundant in the entire population of granule cells. These cells are known to make sparse contacts with dopaminergic axons and also to express the D1 receptor. In the mesencephalon, low levels of D3 messenger RNA were detected in few dopamine neurons of substantia nigra pars lateralis and ventral tegmental area. In addition, some D3 receptor binding but not messenger RNA was detected in medial substantia nigra and lateral ventral tegmental area, where the receptor is presumably located presynaptically on afferents. In the archicerebellum, Purkinje cell perikarya in lobules 9 and 10 expressed the D3 receptor messenger RNA, whereas binding sites were found in the molecular layer, where corresponding dendrites but no known dopaminergic projection from mesencephalon are found. The occurrence of D3 receptor gene expression in some brain areas receiving low dopamine innervation supports the hypothesis that this receptor may mediate non-synaptic actions of dopamine.
Jeancharles Schwartz - One of the best experts on this subject based on the ideXlab platform.
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coexpression of dopamine d1 and d3 receptors in Islands of Calleja and shell of nucleus accumbens of the rat opposite and synergistic functional interactions
1998Co-Authors: Sophie Ridray, Jeancharles Schwartz, Nathalie Griffon, Virginie Mignon, Evelyne Souil, Suzanna Carboni, Jorge Soler A Diaz, Pierre SokoloffAbstract:Using double in situ hybridization, we found extensive coexpression of dopamine D1 and D3 receptor (D1R and D3R) mRNAs in neurons of the island of Calleja major (ICjM) and ventromedial shell of nucleus accumbens (ShV), respectively. Thus, at least 79 and 63% of D3R mRNA-expressing neurons in ICjM and ShV also expressed the D1R mRNA. Coexpression of D1R and D3R mRNAs was found to occur in substance P (SP) mRNA-expressing neurons in both areas, suggesting SP mRNA as a marker of the activity of coexpressing neurons. Administration of SKF 38393, a D1R receptor agonist, increased c-fos mRNA in ICjM, whereas administration of quinpirole, a D2R/D3R agonist, decreased it; SCH 23390, a D1R antagonist and nafadotride, a preferential D3R antagonist, given alone, had effects opposite to those of the corresponding agonists. These data indicate that basal c-fos expression in ICjM is maintained by endogenous dopamine acting tonically upon two receptor subtypes subserving opposite effects on the same cell. However, in ShV, whereas SKF 38393 also increased c-fos mRNA, quinpirole had no effect, a difference presumably reflecting the lower fraction of neurons coexpressing D1R and D3R in this area. In contrast, in ShV from reserpine-treated rats, SKF 38393 increased SP mRNA and quinpirole potentiated this effect. These contrasting interactions of D1R- and D3R-mediated signalling events, i.e. in either opposite or synergistic directions, most likely occurring at the single cell level, may serve to increase the dopamine response threshold of the target cells in ICjM and to maintain a strong tonic activity of ShV neurons.
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d3 dopamine receptor mrna is widely expressed in the human brain
1998Co-Authors: Michio Suzuki, Yasmin L. Hurd, Pierre Sokoloff, Jeancharles Schwartz, Goran SedvallAbstract:Abstract Considerable attention has been given to the association of the D3 dopamine receptor subtype and limbic function based on the abundant localization of D3 receptor sites and mRNA expression in the Islands of Calleja and nucleus accumbens in experimental animals. Though most human anatomical studies have focused on the role of D3 receptors in limited brain structures, detailed information about the overall anatomical organization of the D3 receptor in the human brain is still, however, not available. In the current study, we examined the anatomical distribution of D3 receptor mRNA expression at different levels of the human brain in whole hemisphere horizontal cryosections using in situ hybridization. This approach made it possible to establish for the first time the wide and heterogenous expression of the D3 receptor gene throughout the human brain. As expected, the most abundant D3 mRNA expression levels were found in the Islands of Calleja and discrete cell cluster populations within the ventral striatum/nucleus accumbens region. High levels were also evident within the dentate gyrus and striate cortex. Low to moderate D3 mRNA expression levels were apparent in most brain areas including all other cortical regions (highest in the anterior cingulate/subcallosal gyrus), caudate nucleus, putamen, anterior and medial thalamic nucleus, mammillary body, amygdala, hippocampal CA region, lateral geniculate body, substantia nigra pars compacta, locus coeruleus, and raphe nuclei. While the current anatomical map of D3 receptor mRNA expression in the human brain does confirm previous reports that D3 receptors may play important roles in limbic-related functions such as emotion and cognition, the findings also suggest other non-limbic functions for D3 mRNA-expressing cell populations such as processing of motor and sensory information.
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localization of dopamine d3 receptor mrna in the rat brain using in situ hybridization histochemistry comparison with dopamine d2 receptor mrna
1991Co-Authors: M L Bouthenet, Pierre Sokoloff, Evelyne Souil, Mariepascale Martres, Bruno Giros, Jeancharles SchwartzAbstract:Abstract The messenger RNA (mRNA) of the recently characterized D 3 dopamine receptor was visualized on rat brain sections using in situ hybridization with a 32 P-labeled ribonucleic acid probe corresponding to a major part of the third cytoplasmic loop, a domain in which D 2 and D 3 dopamine receptors display little homology. For the purpose of comparison, D 2 receptor mRNA was also specifically visualized on adjacent sections. The areas that expressed D 2 and/or D 3 receptors were also compared with those previously detected using [ 125 I]iodosulpride, a ligand that binds to both D 2 and D 3 receptors with a similar affinity. The localization of D 3 receptor mRNa markedly differs from that of D 2 receptor mRNA. Whereas D 2 receptor mRNA is expressed in all major brain areas receiving dopaminergic projections, particularly in the whole striatal complex, D 3 receptor mRNA is expressed in a more restricted manner. It is mainly detected in telencephalic areas receiving dopaminergic inputs from the A 10 cell group, e.g. accumbens nucleus, Islands of Calleja, bed nucleus of the stria terminalis and other limbic areas such as the hippocampus and the mammillary nuclei. D 2 and D 3 receptor mRNAs were also detected at the level of the substantia nigra, suggesting that these receptors function as both autoreceptor and postsynaptic receptors. In several dopaminergic projection areas, e.g. ventral striatum, septal or mammillary nuclei, the distribution of D 2 and D 3 receptor mRNAs appeared complementary without overlap. The distribution of [ 125 I]iodosulpride binding sites generally overlapped that of D 2 or D 3 receptor mRNAs, the latter being most abundant in dopaminergic areas known to be associated with cognitive and emotional functions.
David Wirtshafter - One of the best experts on this subject based on the ideXlab platform.
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corrigendum to the distribution of m4 muscarinic acetylcholine receptors in the Islands of Calleja and striatum of rats and cynomolgus monkeys j chem neuroanat 28 2004 107 116
2005Co-Authors: David Wirtshafter, Catherine V OsbornAbstract:Fig. 7. Images of near adjacent sections through Islands of Calleja in the monkey stained for m4-like immunoreactivity (left hand column, panels A and A0) and cresyl violet (panels B and B0). Panels A and B display the insula magna, and it can be seen that m4 staining occupies the cell-sparse core of the island. Panels A0 and B0 show an ordinary island in which the granule cells form a sheet closely applied to the pial surface of the brain (panel B0). In this case, a region of intense m4-like staining is present immediately internal to the granule cell component of the island. Scale bar = 200 mm.
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the distribution of m4 muscarinic acetylcholine receptors in the Islands of Calleja and striatum of rats and cynomolgus monkeys
2004Co-Authors: David Wirtshafter, Catherine V OsbornAbstract:The distribution of m4 muscarinic acetylcholine receptors, and their relation to a number other markers, was examined using immunocytochemical techniques. Staining in the dorsal striatum tended to be more pronounced in the striosomal than the matrix compartment of both rats and cynomolgus monkeys. Within the ventral striatum, immunoreactivity was more pronounced within the olfactory tubercle and the shell region of the nucleus accumbens than in the nucleus accumbens core and was especially marked within the lateral striatal stripe. Modest staining was also seen in the external plexiform layer of the olfactory bulb. By far, the most intense staining in the forebrain of both rats and cynomolgus monkeys was found in Islands of Calleja, where it appeared to be a selective marker for the core or hilus regions of the Islands, or an analogous region found adjacent to them. The core regions of different Islands appear to be continuous with each other so as to form a complex three-dimensional structure, which is largely encased by layers of granule cells. The neuronal elements in the Islands of Calleja, which express m4 receptors, remain to be identified, but it is unlikely that cholinergic neurons are a major locus of these receptors. Although there are certain similarities between the Islands of Calleja and other components of the striatal complex, the current studies emphasize the extent to which the Islands are unique in terms of their architecture and chemical anatomy.
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d1 dopamine receptors mediate neuroleptic induced fos expression in the Islands of Calleja
1998Co-Authors: David WirtshafterAbstract:Systemic injections of the selective, full, D1 agonists A-77636 and SKF-82958 induced pronounced Fos-like immunoreactivity in the Islands of Calleja in the olfactory tubercle of intact rats. Fos expression in this region could also be induced by injections of the D2-like dopamine antagonist raclopride (0.5 mg/kg). Pretreatment with the selective D1 dopamine antagonist SCH-23390 (0.2 mg/kg) completely abolished this response, but was without significant effect on raclopride-induced Fos expression in the dorsolateral region of the striatum. SCH-23390 was also able to prevent the atypical neuroleptic clozapine (30 mg/kg) from inducing Fos expression in the Islands of Calleja. These findings demonstrate that stimulation of D1 dopamine receptors plays an essential role in neuroleptic induction of Fos-like immunoreactivity in the Islands of Calleja, but not in the dorsal striatum, and thus suggest that different mechanisms underlie neuroleptic stimulation of immediate early gene expression in these two structures.
Enrique Lanuza - One of the best experts on this subject based on the ideXlab platform.
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the vomeronasal cortex afferent and efferent projections of the posteromedial cortical nucleus of the amygdala in mice
2014Co-Authors: Nicolas Gutierrezcastellanos, Cecilia Pardobellver, Fernando Martinezgarcia, Enrique LanuzaAbstract:Most mammals possess a vomeronasal system that detects predominantly chemical signals of biological relevance. Vomeronasal information is relayed to the accessory olfactory bulb (AOB), whose unique cortical target is the posteromedial cortical nucleus of the amygdala. This cortical structure should therefore be considered the primary vomeronasal cortex. In the present work, we describe the afferent and efferent connections of the posteromedial cortical nucleus of the amygdala in female mice, using anterograde (biotinylated dextranamines) and retrograde (Fluorogold) tracers, and zinc selenite as a tracer specific for zinc-enriched (putative glutamatergic) projections. The results show that the posteromedial cortical nucleus of the amygdala is strongly interconnected not only with the rest of the vomeronasal system (AOB and its target structures in the amygdala), but also with the olfactory system (piriform cortex, olfactory-recipient nuclei of the amygdala and entorhinal cortex). Therefore, the posteromedial cortical nucleus of the amygdala probably integrates olfactory and vomeronasal information. In addition, the posteromedial cortical nucleus of the amygdala shows moderate interconnections with the associative (basomedial) amygdala and with the ventral hippocampus, which may be involved in emotional and spatial learning (respectively) induced by chemical signals. Finally, the posteromedial cortical nucleus of the amygdala gives rise to zinc-enriched projections to the ventrolateral septum and the ventromedial striatum (including the medial Islands of Calleja). This pattern of intracortical connections (with the olfactory cortex and hippocampus, mainly) and cortico-striatal excitatory projections (with the olfactory tubercle and septum) is consistent with its proposed nature as the primary vomeronasal cortex.
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Vomeronasal inputs to the rodent ventral striatum
2008Co-Authors: Isabel Ubeda-bañon, Alicia Mohedano-moriano, Palma Pro-sistiaga, Enrique Lanuza, Amparo Novejarque, Fernando Martínez-garcía, Ricardo Insausti, Alino Martinez-marcosAbstract:Abstract Vertebrates sense chemical signals through the olfactory and vomeronasal systems. In squamate reptiles, which possess the largest vomeronasal system of all vertebrates, the accessory olfactory bulb projects to the nucleus sphericus, which in turn projects to a portion of the ventral striatum known as olfactostriatum. Characteristically, the olfactostriatum is innervated by neuropeptide Y, tyrosine hydroxylase and serotonin immunoreactive fibers. In this study, the possibility that a structure similar to the reptilian olfactostriatum might be present in the mammalian brain has been investigated. Injections of dextran-amines have been aimed at the posteromedial cortical amygdaloid nucleus (the putative mammalian homologue of the reptilian nucleus sphericus) of rats and mice. The resulting anterograde labeling includes the olfactory tubercle, the Islands of Calleja and sparse terminal fields in the shell of the nucleus accumbens and ventral pallidum. This projection has been confirmed by injections of retrograde tracers into the ventral striato-pallidum that render retrograde labeling in the posteromedial cortical amygdaloid nucleus. The analysis of the distribution of neuropeptide Y, tyrosine hydroxylase, serotonin and substance P in the ventral striato-pallidum of rats, and the anterograde tracing of the vomeronasal amygdaloid input in the same material confirm that, similar to reptiles, the ventral striatum of mammals includes a specialized vomeronasal structure (olfactory tubercle and Islands of Calleja) displaying dense neuropeptide Y-, tyrosine hydroxylase- and serotonin-immunoreactive innervations. The possibility that parts of the accumbens shell and/or ventral pallidum could be included in the mammalian olfactostriatum cannot be discarded.
J M Palacios - One of the best experts on this subject based on the ideXlab platform.
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dopamine d3 receptor mrna and binding sites in human brain
1993Co-Authors: B Landwehrmeyer, G Mengod, J M PalaciosAbstract:Dopamine D3 receptors (Sokoloff et al., 1990) have been shown to be related to dopamine D2 receptors and have been suggested to play a role in mediating the antipsychotic effects of neuroleptics. So far studies on the expression of D3 mRNA and of binding sites with pharmacological characteristics of D3 receptors have been restricted to rat brain. Using in situ hybridization histochemistry, we demonstrate that D3 mRNAs are enriched in human n. accumbens and in the Islands of Calleja. In addition, D3 mRNA was detected at very low levels in anterior caudate and putamen with a rostro-caudally decreasing gradient and in hypothalamic mammillary nuclei. In receptor autoradiographic binding studies, the Islands of Calleja were found to be labeled by [125I]iodosulpride and [3H]CV 205 502 but not by [3H]raclopride and [3H]YM 09151-2. Pharmacological analysis of binding of the D2/D3 ligand [3]H]CV 205 502 in n. accumbens and caudate-putamen is consistent with the presence of D3 receptor sites in ventral striatum. Overall distribution and pharmacology of D3 sites in human and rat brain appear to be similar. Presence and distribution of D3 receptors in human brain are compatible with the notion that D3 receptors might be involved in mediating the clinical effects of antipsychotics.
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differential visualization of dopamine d2 and d3 receptor sites in rat brain a comparative study using in situ hybridization histochemistry and ligand binding autoradiography
1993Co-Authors: B Landwehrmeyer, G Mengod, J M PalaciosAbstract:: At least five members of the dopamine receptor family have been characterized at the gene level. D2, D3 and D4 dopamine receptors are related pharmacologically. In order to visualize the differential expression of D1, D2 and D3 receptors in rat brain we have combined in situ hybridization histochemistry with receptor autoradiography. Regions enriched with D3 messenger RNA (mRNA) included the Islands of Calleja (ioC) and nucleus accumbens. Very low or undetectable levels were present in the caudate-putamen. In contrast, no D2 transcripts were observed in the Islands of Calleja, but there were high levels in the nucleus accumbens, caudate-putamen (CP) and pyramidal layer of the olfactory tubercle. A comparison of the binding pattern of six dopamine receptor radioligands hitherto regarded as D2 receptor-selective showed that the Islands of Calleja were intensely labelled by [125I]iodosulpride, [3H]CV 205 502 and [3H]SDZ 205 501, while the binding of [3H]spiperone, [3H]raclopride and [3H]YM 09151-2 was much lower or undetectable. Pharmacological analysis of the binding of D2/D3 ligands to the Islands of Calleja and caudate-putamen suggests that binding sites in these two regions are of different pharmacology, consistent with the presence of D3 sites in the Islands of Calleja and the predominance of D2 sites in the caudate. These results demonstrate the expression of D3 binding sites in the rat brain and provide a procedure to differentiate D2 and D3 receptor populations in binding studies.
