In view of the therapeutic importance of dopamine D3 and D2 receptors, there remains considerable interest in novel ligands. Herein, we show that the tetrahydroisoquinoline 1H-indole-2carboxylic acid {4-[2-(cyano-3,4-dihydro-1H-isoquinolin-2-yl)ethyl]-cyclohexyl}-amide (SB269,652) behaves as an atypical, allosteric antagonist at D3 and D2 receptors. Accordingly, SB269,652 potently (low nanomola...

The dopamine D3 receptor is expressed primarily in regions of the brain that are thought to influence motivation and motor functions. To specify in vivo D3 receptor function, we generated mutant mice lacking this receptor. Our analysis indicates that in a novel environment, D3 mutant mice are transiently more active than wild-type mice, an effect not associated with anxiety state. Moreover, D3 ...

After the cloning of the dopamine D(1) and D(2) receptors (1-3), several additional dopamine receptors were identified. These new subtypes included the D(3) and D(4) receptors, which are similar to D(2), and the D(5) receptor, which is similar to D(1) (4-6). Although most studies have focused on the role of dopamine D(1) and D(2) receptors in mediating the addictive liability of drugs, the lack...

Luippold, Gerd, Swetlana Schneider, Volker Vallon, Hartmut Osswald, and Bernd Mühlbauer. Postglomerular vasoconstriction induced by dopamine D3 receptor activation in anesthetized rats. Am J Physiol Renal Physiol 278: F570–F575, 2000.—In the present study we investigated the renal hemodynamic effects of dopamine D3 receptor activation by R(1)-7-hydroxy-dipropylaminotetraline (7-OH-DPAT) in thio...

Antagonist and partial agonist modulators of the dopamine D3 receptor (D3R) have emerged as promising therapeutics for the treatment of substance abuse and neuropsychiatric disorders. However, development of druglike lead compounds with selectivity for the D3 receptor has been challenging because of the high sequence homology between the D3R and the dopamine D2 receptor (D2R). In this effort, w...

The dopamine D3 receptor is a class A, rhodopsin-like G protein-coupled receptor that can form dimers and/or higher order oligomers. However, the molecular basis for production of these complexes is not well defined. Using combinations of molecular modeling, site-directed mutagenesis, and homogenous time-resolved FRET, the interfaces that allow dopamine D3 receptor monomers to interact were def...

We have identified 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin ([3H]7-OH-DPAT) as a selective probe for the recently cloned dopamine D3 receptor and used it to assess the presence of this receptor and establish its distribution and properties in brain. In transfected Chinese hamster ovary (CHO) cells, it binds to D3 receptors with subnanomolar affinity, whereas its affinity is approximately 1...

The influence of micronutrients on dopamine systems is not well defined. Using mice, we show a potential role for reduced dietary vitamin D3 (cholecalciferol) in promoting diet-induced obesity (DIO), food intake, and drug consumption while on a high fat diet. To complement these deficiency studies, treatments with exogenous fully active vitamin D3 (calcitriol, 10 µg/kg, i.p.) were performed. No...

Loss of nigrostriatal neurons leads to striatal dopamine deficiency and subsequent development of parkinsonism. The effects of this denervation on D2-like receptors in striatum remain unclear. Most studies have demonstrated increases in striatal dopamine D2-like receptors in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-mediated denervation, but others have found either decrea...