The precise localization of D1 and D2 dopamine receptors within striatal neurons and circuits is crucial information for further understanding dopamine pharmacology. We have used subtype specific polyclonal and monoclonal antibodies against D1 and D2 dopamine receptors to determine their cellular and subcellular distributions, their colocalization, and their differential connectivity with motor...

Dopamine in the nucleus accumbens modulates both motivational and addictive behaviors. Dopamine D1 and D2 receptors are generally considered to exert opposite effects at the cellular level, but many behavioral studies find an apparent cooperative effect of D1 and D2 receptors in the nucleus accumbens. Here, we show that a dopamine-induced enhancement of spike firing in nucleus accumbens neurons...

Stimulation of dopamine D1 receptors has profound effects on addictive behavior, movement control, and working memory. Many of these functions depend on dopaminergic systems in the striatum and D1-D2 dopamine receptor synergies have been implicated as well. We show here that deletion of the D1 dopamine receptor produces a neural phenotype in which amphetamine and cocaine, two addictive psychomo...

Dopamine (DA) receptors play an important role in the modulation of excitability and the responsiveness of neurons to activation of excitatory amino acid receptors in the striatum. In the present study, we utilized mice with genetic deletion of D2 or D4 DA receptors and their wild-type (WT) controls to examine if the absence of either receptor subtype affects striatal excitatory synaptic activi...

OBJECTIVE The aim of our study was to explore the presence and the distribution of D4 dopamine receptors in postmortem human prefrontal cortex, by means of the binding of [3H]YM-09151-2, an antagonist that has equal affinity for D2, D3 and D4 receptors. It was therefore necessary to devise a unique assay method in order to distinguish and detect the D4 component. METHOD Frontal cortex samples...

Dopamine is a key neuromodulatory transmitter in the brain. It acts through dopamine receptors to affect changes in neural activity, gene expression, and behavior. In songbirds, dopamine is released into the striatal song nucleus Area X, and the levels depend on social contexts of undirected and directed singing. This differential release is associated with differential expression of activity-d...

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...

Several dopamine agonists, administered i.m., produced persistent, excessive and non-localized scratching in squirrel monkeys (Saimiri sciureus). Studies were conducted with a series of drugs to determine the pharmacological mechanisms responsible for this effect. All of the dopamine D2 agonists studied produced dose-related increases in scratching, whereas several dopamine D1 receptor agonists...

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...

Typical neuroleptic drugs elicit their antipsychotic effects mainly by acting as antagonists at dopamine D2 receptors. Much of this activity is thought to occur in the cerebral cortex, where D2 receptors are found largely in inhibitory GABAergic neurons. Here we confirm this localization at the electron microscopic level, but additionally show that a subset of cortical interneurons with low or ...