Pharmacological aspects of R-( + )-7-OH-DPAT, a putative dopamine D3 receptor ligand

Damsma, G.; Bottema, Tjibbe; Westerink, Ben H.C.; Tepper, Pieter G.; Dijkstra, Durk; Pugsley, Thomas A.; MacKenzie, Robert G.; Heffner, Thomas G.; Wikström, Håkan

doi:10.1016/0014-2999(93)90533-n

Cited by 124 publications

(62 citation statements)

References 5 publications

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“…In fact, 7-OH-DPAT at a relatively low dose (0.03 -0.3 mg /kg) slightly, but significantly decreased the c-fos mRNA level in the striatum (Fig. 2), which might result from the reduction of striatal dopamine release (23,24). Secondly, it is possible that there is a regional difference in the intracellular effector system coupled to the dopamine D3 receptors.…”

Section: Discussionmentioning

confidence: 95%

7-Hydroxy-N,N’-di-n-propyl-2-aminotetraline, a Preferential Dopamine D3 Agonist, Induces c-fos mRNA Expression in the Rat Cerebellum

Ishibashi¹,

Wakabayashi²,

Ohno³

2002

Japanese Journal of Pharmacology

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ABSTRACT-The effects of a preferential dopamine D3 receptor agonist 7-hydroxy-N,N'-di-n-propyl-2-aminotetralin (7-OH-DPAT) on c-fos mRNA expression in the rat cerebellum were studied by Northern blot analysis. 7-OH-DPAT (0.003 -10 mg /kg, s.c.) markedly increased c-fos mRNA expression in the cerebellum, while its effects in the striatum, nucleus accumbens, and frontal cortex were negligible. The effect of 7-OH-DPAT on cerebellar c-fos mRNA expression was dose-dependent and statistically significant at doses of 0.3 mg /kg or more. A preferential dopamine D2 agonist, bromocriptine (0.01 -3 mg /kg, s.c.), failed to increase c-fos mRNA expression in the cerebellum. The effect of 7-OH-DPAT was blocked by two dopamine D2-type-receptor antagonists, haloperidol and perospirone, but not the D1-type-receptor antagonist SCH23390. Furthermore, dopaminergic denervation by 6-hydroxydopamine did not inhibit but rather potentiated the 7-OH-DPAT-induced c-fos mRNA expression in the cerebellum. These findings suggest that 7-OH-DPAT increases c-fos mRNA expression in the rat cerebellum, probably through postsynaptic dopamine D3 receptor activation.Keywords: 7-OH-DPAT, c-fos, Northern blot, Cerebellum, Dopamine D3 receptorThe dopamine receptors were originally classified as D 1 or D2 based on their differing affinities for various ligands and linkage to intracellular signaling pathways. Recent advances in molecular biology have revealed additional dopamine receptor subtypes. The D3 and D4 receptors, which have homology and similar pharmacological profiles to the D 2 receptor, are considered to belong to the D 2 -typereceptor family. The D5 receptor, which is homologous to the D1 receptor, belongs to the D1-type-receptor family (1). Of the different dopamine receptor subtypes, the dopamine D 3 receptor has been of particular interest, because it has a unique anatomical distribution, i.e., its mRNA is located mainly in the limbic brain areas (e.g., nucleus accumbens, island of Calleja and olfactory tubercle), hypothalamus and cerebellum (2 -4). Pharmacological studies and those using genetically manipulated mice have revealed that the dopamine D 3 receptor regulates locomotor activity, yawning behavior and body temperature (5, 6); however, the biochemical events underlying its physiological role are still to be determined. In addition, although certain cellular events mediated by the dopamine D3 receptor have been reported in transfected cell lines expressing the recombinant receptor (e.g., inhibition of adenylyl cyclase, increased extracellular acidification, alterations in Ca 2+ and K + currents, and the induction of c-fos gene expression (7 -10)), in vivo cellular responses to dopamine D 3 receptor activation have not been demonstrated.The expression of c-fos, an immediate early gene, is known to be a useful in vivo marker for changes in neuronal activity, and it is widely used in mapping cellular signal transduction in the brain (11). In fact, a variety of stimuli, both biological (e.g., pain, stress and seizure) and pharmacologi...

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Section: Discussionmentioning

confidence: 95%

7-Hydroxy-N,N’-di-n-propyl-2-aminotetraline, a Preferential Dopamine D3 Agonist, Induces c-fos mRNA Expression in the Rat Cerebellum

Ishibashi¹,

Wakabayashi²,

Ohno³

2002

Japanese Journal of Pharmacology

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“…Putative D3 dopamine receptor-selective agonists have been used recently in studies of the biochemical properties and physiological roles of D3 receptors (Caine and Koob 1993;Daly and Waddington 1993;Damsma et al 1993;Meller et al 1993). 03 receptors and 02 receptors have similar structural and pharmacological properties (Sokoloff et al 1990).…”

Section: Discussionmentioning

confidence: 99%

“…The identification of 7-OH-DPAT as a 03 receptorselective drug has stimulated the use of this agent in laboratory animals to identify functional responses mediated by 03 receptors (Caine and Koob 1993;Daly and Waddington 1993;Damsma et al 1993). However, the validity of using 7-OH-DPAT -or other agoniststo discriminate between effects mediated by D2 and 03 receptors is problematic.…”

Section: Quinpirole When Receptors Were Labeled With the D2 Receptormentioning

confidence: 99%

Lack of Discrimination by Agonists for D2 and D3 Dopamine Receptors

Burris

Pacheco

Filtz

et al. 1995

Neuropsychopharmacology

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“…Introduction 7-OH-DPAT ((± )-7-hydroxy-N,N-di-«-propyl"2-amino tetralin) has been found to act as a selective agonist at dopamine D^ receptors in a variety of studies (biochemical studies: Rivet et al, 1994;Sokoloff et al, 1990; electrophysiological studies: Kreiss et al, 1995; behavioural stud ies: Daly and Waddington, 1993;Damsma et al, 1993;Svensson et al, 1994;Waters et alM 1993). However, later studies have demonstrated that 7-OH-DPAT may be less selective than originally claimed (biochemical studies: Gonzalez and Sibley, 1995;electrophysiological studies: Corresponding author.…”

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confidence: 99%

Behavioural effects of 7-OH-DPAT are solely due to stimulation of dopamine D2 receptors in the shell of the nucleus accumbens; turning behaviour

Koshikawa

Kitamura

Kobayashi

et al. 1996

European Journal of Pharmacology

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The goal of this study was to determine whether the dopamine D3 receptor in limbic structures plays a role in the shell-specific and dopamine-dependent display of turning behaviour in rats. When combined with the dopamine receptor agonist (± )-i-phenyl-2,3,4,5-tetrahydro-1 //-3-benzazepine-7,8-diol (SKF-38393, 5 jx g ) , the putative dopamine D3 receptor agonist (±)-7-hydroxy-/V,N-di-n-propyl-2-aminotetralin (7-OH-DPAT, 1, 5 and 10 jJLg) elicited contralateral turning in a dose-dependent manner following unilateral injection into the shell, but not the core, of the nucleus accumbens. The turning pattern displayed was identical to that reported previously after intra-accumbens administration of the cocktail of SKF-38393 and the dopamine D2 receptor agonist quinpirole. The behaviour under study was dose-dependently attenuated by local administration of the dopamine Dj receptor antagonist /?(-h)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1//-3-benzazepi ne (SCH 23390: 10 and 100 ng), the dopamine D2 receptor antagonist domperidone (25 and 50 ng) or the dopamine D2/3 receptor antagonist /-sulpiride (5 and 25 ng). Combined blockade of both dopamine Dj and D2 receptors in the shell with a dose of either antagonist alone that produced just a moderate reduction (10 ng SCH 23390 and 50 ng domperidone) completely antagonized the turning behaviour elicited by the cocktail of SKF-38393 and 7-OH-DPAT. Replacing 7-OH-DPAT by another putative dopamine D3 receptor agonist, 5( + )-(4a/?,10W?)-3,4,4tf,10£~tetrahydro-4-propyl-2tf,5//-[l]benzopyrano [4,[3][4][5][6]907, 10 jxg), in the cocktail did produce no turning behaviour at all. It is concluded that mesolimbic dopamine D3 receptors play no role in the dopamine-dependent and shell-specific turning behaviour: the contribution of 7-OH-DPAT in the cocktail of SKF-38393 and 7-OH-DPAT to the display of turning behaviour is solely due to its ability to activate dopamine D2 receptors,

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Pharmacological aspects of R-( + )-7-OH-DPAT, a putative dopamine D3 receptor ligand

Cited by 124 publications

References 5 publications

7-Hydroxy-N,N’-di-n-propyl-2-aminotetraline, a Preferential Dopamine D3 Agonist, Induces c-fos mRNA Expression in the Rat Cerebellum

7-Hydroxy-N,N’-di-n-propyl-2-aminotetraline, a Preferential Dopamine D3 Agonist, Induces c-fos mRNA Expression in the Rat Cerebellum

Lack of Discrimination by Agonists for D2 and D3 Dopamine Receptors

Behavioural effects of 7-OH-DPAT are solely due to stimulation of dopamine D2 receptors in the shell of the nucleus accumbens; turning behaviour

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