Research article summary (published 27 Feb 1999):

Blockade of neurotensin receptors suppresses the dopamine D1/D2 synergism on immediate early gene expression in the rat brain.

Full Abstract

A remarkable feature of dopamine functioning is that the concomitant activation of D1-like and D2-like receptors acts to intensify the expression of various dopamine-dependent effects, in particular the expression of the immediate-early genes, c-fos and zif268. Using non-peptide neurotensin receptor antagonists, including SR48692, we have determined that blockade of neurotensin receptors reduced the cooperative responses of direct acting D2-like (quinpirole) and partial D1-like (SKF38393) dopamine agonists on the expression of Fos-like antigens and zif268 mRNA. Pretreatment with SR48692 (3 and 10 mg/kg) reduced the number of Fos-like immunoreactive cells produced by the combined administration of SKF38393 (20 mg/kg) and quinpirole (1 mg/kg) in the caudate-putamen, nucleus accumbens, globus pallidus and ventral pallidum. High-affinity neurotensin receptors are likely to be involved in these D1-like/D2-like cooperative responses, as compounds structurally related to SR48692, SR48527 (3 mg/kg) and its (-)antipode, SR49711 (3 mg/kg), exerted a stereospecific antagonism in all selected brain regions. Pretreatment with SR48692 (10 mg/kg) also diminished Fos induction by the indirect dopamine agonist, cocaine (25 mg/kg), particularly at the rostral level of the caudate-putamen. In situ hybridization experiments in the caudate-putamen indicated that SR48692 (10 mg/kg) markedly reduced zif268 mRNA labelling produced by SKF38393 plus quinpirole in cells not expressing enkephalin mRNA, but was unable to affect the concomitant decrease of zif268 mRNA labelling in enkephalin-positive cells. Taken together, the results of the present study indicate that neurotensin is a key element for the occurrence of cooperative responses of D2-like and partial D1-like agonists on immediate-early gene expression.

Author information

Author/s: Alonso, R (R); Gnanadicom, H (H); Fréchin, N (N); Fournier, M (M); Le Fur, G (G); Soubrié, P (P);

Affiliation: Sanofi Recherche, Department of Neuropsychiatry, 371 rue du Pr. J. Blayac, 34184 Montpellier Cedex 04, France. richard.aloso(-atsign-)tls.elfsanofi.fr

Journal and publication information

Publication Type: Journal Article

Journal: The European journal of neuroscience (Eur J Neurosci), published in FRANCE. (Language: eng)

Reference: 1999-Mar; vol 11 (issue 3) : pp 967-74

Dates: Created 1999/04/26; Completed 1999/04/26; Revised 2005/11/17;

PMID: 10103090, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine - pharmacology Animals Brain Chemistry - physiology Cocaine - pharmacology DNA-Binding Proteins - genetics Dopamine Agonists - pharmacology Dopamine Uptake Inhibitors - pharmacology Early Growth Response Protein 1 Enkephalins - analysis Gene Expression - drug effects; physiology Genes, Immediate-Early - physiology Immediate-Early Proteins In Situ Hybridization Male

Male Neostriatum - chemistry; cytology; physiology Neurons - chemistry; drug effects; physiology Proto-Oncogene Proteins c-fos - genetics Pyrazoles - pharmacology Quinolines - pharmacology Quinpirole - pharmacology RNA, Messenger - analysis Rats Rats, Sprague-Dawley Receptors, Dopamine D1 - physiology Receptors, Dopamine D2 - physiology Receptors, Neurotensin - antagonists & inhibitors Transcription Factors - genetics

Associated Chemicals: DNA-Binding Proteins (0) ; Dopamine Agonists (0) ; Dopamine Uptake Inhibitors (0) ; Early Growth Response Protein 1 (0) ; Egr1 protein, rat (0) ; Enkephalins (0) ; Immediate-Early Proteins (0) ; Proto-Oncogene Proteins c-fos (0) ; Pyrazoles (0) ; Quinolines (0) ; RNA, Messenger (0) ; Receptors, Dopamine D1 (0) ; Receptors, Dopamine D2 (0) ; Receptors, Neurotensin (0) ; SR 142948 (0) ; SR 48527 (0) ; Transcription Factors (0) ; SR 48692 (146362-70-1) ; Cocaine (50-36-2) ; 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine (67287-49-4) ; Quinpirole (85760-74-3)

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