title: Effect of acute and continuous morphine treatment on transcription factor expression in subregions of the rat caudate putamen. Marked modulation by D4 receptor activation.
abstract: Acute administration of the dopamine D(4) receptor (D(4)R) agonist PD168,077 induces a down-regulation of the μ opioid receptor (MOR) in the striosomal compartment of the rat caudate putamen (CPu), suggesting a striosomal D(4)R/MOR receptor interaction in line with their high co-distribution in this brain subregion. The present work was designed to explore if a D(4)R/MOR receptor interaction also occurs in the modulation of the expression pattern of several transcription factors in striatal subregions that play a central role in drug addiction. Thus, c-Fos, FosB/ΔFosB and P-CREB immunoreactive profiles were quantified in the rat CPu after either acute or continuous (6-day) administration of morphine and/or PD168,077. Acute and continuous administration of morphine induced different patterns of expression of these transcription factors, effects that were time-course and region dependent and fully blocked by PD168,077 co-administration. Moreover, this effect of the D(4)R agonist was counteracted by the D(4)R antagonist L745,870. Interestingly, at some time-points, combined treatment with morphine and PD168,077 substantially increased c-Fos, FosB/ΔFosB and P-CREB expression. The results of this study give indications for a general antagonistic D(4)R/MOR receptor interaction at the level of transcription factors. The change in the transcription factor expression by D(4)R/MOR interactions in turn suggests a modulation of neuronal activity in the CPu that could be of relevance for drug addiction.
authors.affiliation: Department of Cell Biology, School of Science, University of Málaga, 29071 Málaga, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Gago
authors.forename: Diana
authors.initials: D
authors.lastname: Suárez-Boomgaard
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
authors.forename: Stefan
authors.initials: S
authors.lastname: Brené
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Reina-Sánchez
authors.forename: Luis M
authors.initials: LM
authors.lastname: Rodríguez-Pérez
authors.forename: Luigi F
authors.initials: LF
authors.lastname: Agnati
authors.forename: Adelaida
authors.initials: A
authors.lastname: de la Calle
authors.forename: Alicia
authors.initials: A
authors.lastname: Rivera
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001549:Benzamides / Q000494:pharmacology; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D016762:Genes, fos / Q000187:drug effects; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D011699:Putamen / Q000187:drug effects / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050638:Receptors, Dopamine D4 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D014157:Transcription Factors / Q000096:biosynthesis*
chemical_list: C099630:3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo(2,3-b)pyridine; D000701:Analgesics, Opioid; D001549:Benzamides; D017362:Cyclic AMP Response Element-Binding Protein; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; C477501:N-((4-(2-cyanophenyl)-1-piperazinyl)methyl)-3-methylbenzamide; D010879:Piperazines; D016760:Proto-Oncogene Proteins c-fos; D011725:Pyridines; D011758:Pyrroles; D014157:Transcription Factors; D050638:Receptors, Dopamine D4; D009020:Morphine