D1 and D2 dopamine receptor gene expression in the rat striatum: Sensitive cRNA probes demonstrate prominent segregation of D1 and D2 mRNAS in distinct neuronal populations of the dorsal and ventral striatum

The postsynaptic effects of dopamine in the striatum are mediated mainly by receptors encoded by D1, D2, and D3 dopamine receptor genes. The D1 and D2 genes are the most widely expressed in the caudate‐putamen, the accumbens nucleus, and the olfactory tubercle. Several anatomical studies, including studies using in situ hybridization with oligonucleotide and cDNA probes, have suggested that D1 and D2 receptors are segregated into distinct efferent neuronal populations of the striatum: D1 in substance P striatonigral neurons and D2 in enkephalin striatopallidal neurons. In contrast, on the basis of several in vivo and in vitro studies, other authors have suggested the existence of an extensive colocalization of D1 and D2 in the same striatal neurons. Our study was undertaken in order to analyze in detail the expression of the D1 and D2 receptor genes in the efferent striatal populations, with special reference to the various striatal areas, and to yield insights into the question about D1 and D2 mRNA localization in the striatum. We have, therefore, used highly sensitive digoxigenin‐and 35S‐labeled cRNA probes to address this question. The present results demonstrate that the D1 and D2 receptor mRNAs are segregated, respectively, in substance P and enkephalin neurons in the caudate‐putamen and accumbens nucleus (shell and core) and in the olfactory tubercle (for their largest part). A very small percentage of neurons may coexpress both genes. These results confirm that the D1 and D2 receptor genes are expressed in distinct populations of striatal efferent neurons in the normal adult rat. © 1995 Wiley‐Liss, Inc.

[1]  J. Kebabian,et al.  Multiple receptors for dopamine , 1979, Nature.

[2]  D. Sibley,et al.  The classification of dopamine receptors: relationship to radioligand binding. , 1983, Annual review of neuroscience.

[3]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[4]  K. Yoshikawa,et al.  Rat brain preproenkephalin mRNA. cDNA cloning, primary structure, and distribution in the central nervous system. , 1984, The Journal of biological chemistry.

[5]  D. Kooy,et al.  Dopamine and opiate receptors: Localization in the striatum and evidence for their axoplasmic transport in the nigrostriatal and striatonigral pathways , 1986, Neuroscience.

[6]  B. Bloch,et al.  In situ hybridization histochemistry for the analysis of gene expression in the endocrine and central nervous system tissues: A 3‐year experience , 1986, Journal of neuroscience research.

[7]  M. Savasta,et al.  Autoradiographic distribution of the D1 agonist [3H]SKF 38393, in the rat brain and spinal cord. Comparison with the distribution of D2 dopamine receptors , 1986, Neuroscience.

[8]  M. Chesselet,et al.  Comparative distribution of mRNAs for glutamic acid decatrboxylase, tyrosine hydroxylase, and tachykinins in the basal ganglia: An in situ hybridization study in the rodent brain , 1987, The Journal of comparative neurology.

[9]  R. M. Beckstead.  Association of dopamine d, and d2 receptors with specific cellular elements in the basal ganglia of the cat: The uneven topography of dopamine receptors in the striatum is determined by intrinsic striatal cells, not nigrostriatal axons , 1988, Neuroscience.

[10]  C. Gerfen,et al.  Distribution of striatonigral and striatopallidal peptidergic neurons in both patch and matrix compartments: an in situ hybridization histochemistry and fluorescent retrograde tracing study , 1988, Brain Research.

[11]  C. Gerfen,et al.  Multiple D2 dopamine receptors produced by alternative RNA splicing , 1989, Nature.

[12]  J. Penney,et al.  The functional anatomy of basal ganglia disorders , 1989, Trends in Neurosciences.

[13]  C. Gerfen,et al.  D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. , 1990, Science.

[14]  A. Graybiel.  Neurotransmitters and neuromodulators in the basal ganglia , 1990, Trends in Neurosciences.

[15]  G. Wooten,et al.  Selective localization of striatal D1 receptors to striatonigral neurons , 1990, Brain Research.

[16]  A. Reiner,et al.  The patterns of neurotransmitter and neuropeptide co-occurrence among striatal projection neurons: conclusions based on recent findings , 1990, Brain Research Reviews.

[17]  P. Greengard,et al.  Inhibition by dopamine of (Na+ + K+)ATPase activity in neostriatal neurons through D1 and D2 dopamine receptor synergism , 1990, Nature.

[18]  C. Wilson,et al.  Projection subtypes of rat neostriatal matrix cells revealed by intracellular injection of biocytin , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[19]  H. Akil,et al.  Comparison of the distributions of D1 and D2 dopamine receptor mRNAs in rat brain. , 1991, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[20]  C. Gerfen.  Substance P (neurokinin-1) receptor mRNA is selectively expressed in cholinergic neurons in the striatum and basal forebrain , 1991, Brain Research.

[21]  M. Chesselet,et al.  Heterogeneous distribution of dopamine D2 receptor mRNA in the rat striatum: A quantitative analysis with in situ hybridization histochemistry , 1991, The Anatomical record.

[22]  E. Unger,et al.  Comparison of 35S and biotin as labels for in situ hybridization: use of an HPV model system. , 1991, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[23]  S. Schiffmann,et al.  Striatal Restricted Adenosine A2 Receptor (RDC8) Is Expressed by Enkephalin but Not by Substance P Neurons: An In Situ Hybridization Histochemistry Study , 1991, Journal of neurochemistry.

[24]  B. Bloch,et al.  Simultaneous detection of two messenger RNAs in the central nervous system: a simple two-step in situ hybridization procedure using a combination of radioactive and non-radioactive probes. , 1991, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[25]  Bruno Giros,et al.  Localization of dopamine D3 receptor mRNA in the rat brain using in situ hybridization histochemistry: comparison with dopamine D2 receptor mRNA , 1991, Brain Research.

[26]  B. Bloch,et al.  Striatal neurons express increased level of dopamine D2 receptor mRNA in response to haloperidol treatment: A quantitative in situ hybridization study , 1991, Neuroscience.

[27]  M. Martres,et al.  Dopamine activation of the arachidonic acid cascade as a basis for D1D2 receptor synergism , 1991, Nature.

[28]  W. Young,et al.  Spatial and temporal expression of alpha- and beta-thyroid hormone receptor mRNAs, including the beta 2-subtype, in the developing mammalian nervous system , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[29]  H. Fibiger,et al.  D1 and D2 dopamine receptors differentially regulate c-fos expression in striatonigral and striatopallidal neurons , 1992, Neuroscience.

[30]  D. Sibley,et al.  D2 dopamine receptor localization on striatonigral neurons , 1992, Neuroscience Letters.

[31]  G. Wooten,et al.  Differential regulation of striatal preproenkephalin mRNA by D1 and D2 dopamine receptors. , 1992, Brain research. Molecular brain research.

[32]  C. Gerfen.  The neostriatal mosaic: multiple levels of compartmental organization in the basal ganglia. , 1992, Annual review of neuroscience.

[33]  M. Herkenham,et al.  Influence of a single injection of cocaine, amphetamine or GBR 12909 on mRNA expression of striatal neuropeptides. , 1992, Brain research. Molecular brain research.

[34]  R. Wiley,et al.  Changes in D2 but not D1 receptor binding in the striatum following a selective lesion of striatopallidal neurons , 1992, Brain Research.

[35]  D. Sibley,et al.  Molecular biology of dopamine receptors. , 1992, Trends in pharmacological sciences.

[36]  D. Sibley,et al.  D2 dopamine receptor distribution in the rodent CNS using anti-peptide antisera , 1993, Brain Research.

[37]  G. Wooten,et al.  Differential localization of A2a adenosine receptor mRNA with D1 and D2 dopamine receptor mRNA in striatal output pathways following a selective lesion of striatonigral neurons , 1993, Brain Research.

[38]  Stephen J. Fink,et al.  Colocalization of D1 and D2 dopamine receptor mRNAs in striatal neurons , 1993, Brain Research.

[39]  R. Harlan,et al.  Ontogeny of the proenkephalin system in the rat corpus striatum: Its relationship to dopaminergic innervation and transient compartmental expression , 1993, Neuroscience.

[40]  J. Morrison,et al.  Heterogeneous distribution of D1, D2 and D5 receptor mRNAs in monkey striatum , 1993, Brain Research.

[41]  J. Vanderhaeghen,et al.  Adenosine A2 receptors regulate the gene expression of striatopallidal and striatonigral neurons , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[42]  P. Strange.  Dopamine receptors: structure and function. , 1993, Progress in brain research.

[43]  S. Augood,et al.  Neuroleptics and striatal neuropeptide gene expression. , 1993, Progress in brain research.

[44]  C. Gerfen,et al.  Cocaine-induced c-fos messenger RNA is inversely related to dynorphin expression in striatum , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[45]  D. Surmeier,et al.  Are neostriatal dopamine receptors co-localized? , 1993, Trends in Neurosciences.

[46]  S. Sesack,et al.  Ultrastructural localization of D2 receptor-like immunoreactivity in midbrain dopamine neurons and their striatal targets , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[47]  C. Moine,et al.  Delta-opioid receptor gene expression in the mouse forebrain: Localization in cholinergic neurons of the striatum , 1994, Neuroscience.