Dopamine D1 ligands have been classified and ordered according to efficacy in both in vitro and in vivo studies. In the present experiments, dopamine D1 ligands reported to differ in in vitro efficacy were evaluated for efficacy-related effects on eye blinking in squirrel monkeys. Additional comparisons were made with the effects of D2 receptor agonists and indirect dopamine agonists. The resul...

BACKGROUND AND HYPOTHESIS It is well known that after prolonged abstinence, individuals who use their drug of choice experience a powerful euphoria that often precipitates relapse. While a biological explanation for this conundrum has remained elusive, we hypothesize that this clinically observed "supersensitivity" might be tied to genetic dopaminergic polymorphisms. Another therapeutic conundr...

Although it is commonly stated that phencyclidine is an antagonist at ionotropic glutamate receptors, there has been little measure of its potency on other receptors in brain tissue. Although we previously reported that phencyclidine stimulated cloned-dopamine D2Long and D2Short receptors, others reported that phencyclidine did not stimulate D2 receptors in homogenates of rat brain striatum. Th...

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...

BACKGROUND The interaction between the dopaminergic and somatostatinergic systems and their role in mood regulation have been well-documented. Therefore, we decided to investigate the effect of antidepressant drugs on the heterodimerization of the dopamine D2 and somatostatin Sst5 receptors. METHODS The human receptor proteins were tagged with fluorescent proteins, expressed in the HEK 293 ce...

Acute activation of Galpha(i/o)-coupled D2 dopamine receptors inhibits A2A adenosine receptor stimulation of adenylate cyclase. This antagonistic interaction between D2 dopamine and A2A adenosine receptors has been well documented; however, the effects of persistent activation of D2 dopamine receptors on subsequent A2A adenosine receptor signaling have not been explored. The present study inves...

In pituitary lactotrophs the prolactin gene is stimulated by neuropeptides and estrogen and is suppressed by dopamine via D2-type receptors. Stimulatory signals converge on activation of the mitogen-activated protein kinases ERK1/2, but dopamine regulation of this pathway is not well defined. Paradoxically, D2 agonists activate ERK1/2 in many cell types. Here we show that in prolactin-secreting...

Substantia nigra (SN) dopamine neurons express D2 and D3 dopamine autoreceptors. A physiological role for the D3 receptor has not been identified, but an activation of G-protein-gated inwardly rectifying potassium (GIRK; also known as Kir3) channels is strongly implicated because D3 receptors activate channels composed of GIRK2 subunits in cell lines. We confirmed that acutely dissociated SN do...

In the rat, selective suppression of conditioned avoidance response has been widely reported as a test with high predictive validity for antipsychotic efficacy. Recent studies have shown that the relationship between dopamine D2 receptor occupancy and the suppression of conditioned avoidance response behaviour correlates well with the relationship between human dopamine D2 receptor occupancy an...

previous studies have shown that ascorbic acid (aa) plays a crucial role in mammalian brain as avitamin and neuronal modulator. there is increasing evidence indicating that dopaminergic system and aacould affect learning and memory processes. in addition, vitamin c acts as a dopamine antagonist in thebrain. the aim of the present study was to evaluate the intra-hippocampal co-administration of ...