Dopaminergic component of [3H]spiroperidol binding in the rat anterior cerebral cortex

Marchais, Dominique; Tassin, Jean‐Pol; Bockaert, Joël

doi:10.1016/0006-8993(80)90136-5

Cited by 50 publications

(8 citation statements)

References 11 publications

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“…In the D2 binding system, which appeared to have a dopaminergic distribution in tissue areas (i.e., sites detectable only in regions with dopaminergic innervation), binding isotherms and Scatchard plots became monophasic and revealed similar low Kd values (0.05-0.1 nM) in areas where the D2 site was present. Although it may seem surprising that no D2 sites were detected in the frontal cortex, the present results are consistent with those of other workers, who have failed to detect dopaminergic [3H]spiperone binding in whole frontal cortex (6,9,10); when dopaminergic areas of the frontal cortex are specifically dissected out, however, D2-type binding is detected (17 (20 …”

supporting

confidence: 82%

Resolution of dopamine and serotonin receptor components of [3H]spiperone binding to rat brain regions.

List¹,

Seeman²

1981

Proc. Natl. Acad. Sci. U.S.A.

117

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A procedure was developed to identify receptors for dopamine and serotonin separately and selectively by means of [3H]spiperone and to measure the density of each receptor in different regions of the rat brain. In the striatum, the binding of [3H]spiperone to dopamine receptors was inhibited by sulpiride but not by quinazolinedone R43448 (R43448); in the frontal cortex, however, the binding of [3H]spiperone to serotonin receptors was inhibited by R43448 but not by sulpiride. Thus, the density of dopamine receptors (D2 sites) was measured by [3H]spiperone binding in the presence of 0.1 microM R43448 (to preclude the attachment of the 3H-labeled ligand to serotonin sites), while the density of serotonin receptors (S2 sites) was measured by [3H]spiperone binding in the presence of 10 microM sulpiride (to preclude the attachment of the 3H-labeled ligand to dopamine sites). The density of D2 sites was highest in the striatum, followed by the olfactory tubercle, hypothalamus, substantia nigra, and the lower pons--medulla region. All five regions had similar dissociation constants (Kd values) of 0.05--0.15 nM. The density of S2 sites was highest in the frontal cortex, followed by the posterior cortex, olfactory tubercle, striatum, hypothalamus, and thalamus, and all regions had Kd values in the range 0.6--2.3 nM. Thus, because the Kd values were similar for all regions, and because Scatchard analyses revealed a single set of sites for either D2 or S2 (where detected), the main criteria for resolving the dopamine and serotonin components of [3H]spiperone binding were considered fulfilled.

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supporting

confidence: 82%

Resolution of dopamine and serotonin receptor components of [3H]spiperone binding to rat brain regions.

List¹,

Seeman²

1981

Proc. Natl. Acad. Sci. U.S.A.

117

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“…38 The same effect can be produced by endogenous DA, as evidenced by the suppression of PFC discharge in response to the VTA stimulation. 39,40 Although both D1-like and D2-like receptors are present in the PFC, 43,44 the suppressant effect of DA was shown to be mediated by the latter, as selective blockade of D2-like but not D1-like receptors reversed this action. 29,41 It was previously documented that the PPX-induced activation of somatodendritic D2 autoreceptors in the VTA led to the decrease in the firing rate of DA neurons, driven by the negative feedback mechanism exerted by the cell body D2 auto receptors.…”

Section: Discussionmentioning

confidence: 99%

Long-term administration of the dopamine D3/2 receptor agonist pramipexole increases dopamine and serotonin neurotransmission in the male rat forebrain

Chernoloz

Mansari

Blier

2012

J Psychiatry Neurosci

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“…The receptor population defined as site A comprises only 25% of the total, making these sites the more likely candidates to be receptors for 5-HT. Site A, however, had a higher affinity for dopamine than (27). In addition, receptors in the frontal cortex have 1/60th the affinity for domperidone compared to either of the two classes of striatal sites.…”

mentioning

confidence: 96%

Quantitative determination of dopamine receptor subtypes not linked to activation of adenylate cyclase in rat striatum.

Huff¹,

Molinoff²

1982

Proc. Natl. Acad. Sci. U.S.A.

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It is unlikely that either of the two classes of striatal sites are receptors for serotonin. The approach described will make it possible to assess the effects of physiological or pharmacological manipulations on the densities or properties of subtypes of dopamine receptors.The striatum is thought to contain multiple subtypes of dopamine receptors. Kebabian et aL (1) characterized a dopaminesensitive adenylate cyclase activity in the striatum. In vitro binding assays using the butyrophenones [3H]haloperidol and [3H]spiroperidol also revealed the presence of dopamine receptors in this brain region (2-4). However, the properties and distribution of the binding sites for butyrophenones differed from those expected based on studies of dopamine-sensitive adenylate cyclase activity (5-7). A classification scheme was developed such that the subtypes ofdopamine receptors whose effects involved activation of adenylate cyclase were called D-1 receptors and receptors not linked to stimulation of the enzyme were called D-2 receptors (8).Guanine nucleotides decreased the affinity of [3H]spiroperidol binding sites in the striatum for agonists (9). By analogy to other receptor systems that are linked to activation of adenylate cyclase (10-12), we suggested that some of the sites labeled by[3H]spiroperidol were also linked to stimulation ofthis enzyme. METHODSThe striatum or frontal cortex from male Sprague-Dawley rats was homogenized in 35 ml of 20 mM Hepes, pH 7.5/154 mM NaCl/5 mM EDTA. After centrifugation (20,000 X g for 10 min at 4°C) pellets were resuspended in 20 mM Hepes, pH 7.5/ 154 mM NaCI, incubated at 37°C for 15 min, and recentrifuged. Striatal membranes were resuspended in 20 mM Hepes/154 mM NaCl at a concentration of 2-4 mg of tissue per ml for studies of [3H]domperidone binding, 1-2 mg/ml for studies of [3H]spiroperidol binding in the striatum, and 4 mg/ml for studies of [3H]spiroperidol binding in frontal cortex.[3H]Domperidone (59.7 Ci/mmol; 1 Ci = 3.7 X 1010 becquerels), [3H]spiroperidol (29.9 Ci/mmol), drugs, and GTP (final concentration, 0.3 mM) were diluted in 2.6 mM ascorbic acid containing 20 ,ug of bovine serum albumin per ml.Binding reactions were carried out for 45 min at 37°C and then terminated by the addition of 10 ml ofice-cold 10 mM Tris, pH 7.5/154 mM NaCl. Samples were filtered through glass fiber filters (Schleicher & Schuell,no. 30) and washed with an additional 10 ml of the same buffer. Specific binding was defined as the difference between the amount of radioligand bound in the presence and absence of 2 ,uM (+) butaclamol. Protein content was determined by the method ofBradford (20).The untransformed data obtained in studies of the binding of [3H]domperidone were analyzed by nonlinear regression analysis using the computer modeling program SAAM27. The data were compared to model curves describing one, two, and three sites, and F-test analysis was used to determine the most appropriate model (21). Regression analysis of linear Scatchard, Hill, and Hofstee plots was carried out by the leas...

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Dopaminergic component of [3H]spiroperidol binding in the rat anterior cerebral cortex

Cited by 50 publications

References 11 publications

Resolution of dopamine and serotonin receptor components of [3H]spiperone binding to rat brain regions.

Resolution of dopamine and serotonin receptor components of [3H]spiperone binding to rat brain regions.

Long-term administration of the dopamine D3/2 receptor agonist pramipexole increases dopamine and serotonin neurotransmission in the male rat forebrain

Quantitative determination of dopamine receptor subtypes not linked to activation of adenylate cyclase in rat striatum.

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