title: Effect of raclopride on dopamine D2 receptor mRNA expression in rat brain.
abstract: Prolonged treatment with dopamine D2 receptor antagonists is known to elevate the density of dopamine D2 receptor binding sites in caudate-putamen and nucleus accumbens in rat and human brain. In this study we used the dopamine D2 receptor antagonist raclopride (3 mumol/kg, s.c.) to determine if a single injection or daily administration of this drug for up to 18 days changed the expression of dopamine D2 receptor mRNA in rat caudate-putamen and accumbens as measured by in situ hybridization. A single injection of raclopride did not significantly change the numerical density of dopamine D2 receptor mRNA-expressing neurons in any of the regions examined. A daily administration of raclopride for 18 days resulted in a 31% increase in the number of cells expressing detectable amounts of dopamine D2 receptor mRNA in dorsolateral caudate-putamen and in a 20% increase in the area of silver grains over individual hybridization-positive neurons in this brain region measured on emulsion-dipped slides. The region-specific increase in the D2 receptor mRNA level in dorsolateral caudate-putamen was confirmed by measurement of the hybridization signal on X-ray film autoradiograms. The levels of D2 receptor mRNA remained unchanged in medial caudate-putamen and accumbens after 18 days' treatment. The region-selective increase in dopamine D2 receptor mRNA expression in dorsolateral caudate-putamen indicates a differential regulation of dopamine D2 receptor mRNA expression in a subpopulation of caudate-putamen neurons by this neuroleptic. We suggest that the increase in dopamine D2 receptor density in caudate-putamen known to follow prolonged dopamine D2 receptor blockade to some extent is regulated at the level of gene expression.
authors.affiliation: Department of Psychiatry and Psychology, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Kopp
authors.forename: N
authors.initials: N
authors.lastname: Lindefors
authors.forename: S
authors.initials: S
authors.lastname: Brené
authors.forename: H
authors.initials: H
authors.lastname: Hall
authors.forename: H
authors.initials: H
authors.lastname: Persson
authors.forename: G
authors.initials: G
authors.lastname: Sedvall
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D001483:Base Sequence; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D018492:Dopamine Antagonists; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020891:Raclopride; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000235:genetics*; D017448:Receptors, Dopamine D2; D012457:Salicylamides / Q000494:pharmacology*; D013462:Sulfur Radioisotopes
chemical_list: D018492:Dopamine Antagonists; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D013462:Sulfur Radioisotopes; D020891:Raclopride