Search results for " Dopamine D2"
showing 10 items of 63 documents
Synthesis and evaluation in rats of the dopamine D2/3 receptor agonist 18F-AMC20 as a potential radioligand for PET
2015
Dopamine D2/3 receptor (D2/3R) agonist PET tracers are better suited for the imaging of synaptic dopaminergic neurotransmission than D2/3R antagonists and may also offer the opportunity to study in vivo the high-affinity state of D2/3R (D2/3RHigh). With the aim to develop 18F-labeled D2/3R agonists suitable for widespread clinical application, we report here on the synthesis and in vitro and in vivo evaluation of a D2/3R agonist ligand from the aminomethyl chromane (AMC) class-(R)-2-[(4- 18Fluorobenzylamino)methyl]chroman-7-ol (18F-AMC20). Methods: In vitro affinities of AMC20 toward dopaminergic receptor subtypes were measured in membrane homogenates prepared from HEK293 cells expressing h…
Involvement of Dopamine D2 Receptors in Addictive-Like Behaviour for Acetaldehyde
2014
Acetaldehyde, the first metabolite of ethanol, is active in the central nervous system, where it exerts motivational properties. Acetaldehyde is able to induce drinking behaviour in operant-conflict paradigms that resemble the core features of the addictive phenotype: drug-intake acquisition and maintenance, drug-seeking, relapse and drug use despite negative consequences. Since acetaldehyde directly stimulates dopamine neuronal firing in the mesolimbic system, the aim of this study was the investigation of dopamine D2-receptors' role in the onset of the operant drinking behaviour for acetaldehyde in different functional stages, by the administration of two different D2-receptor agonists, q…
Tetrahydroisoquinolines as dopaminergic ligands: 1-Butyl-7-chloro-6-hydroxy-tetrahydroisoquinoline, a new compound with antidepressant-like activity …
2009
International audience; Three series of 1-substituted-7-chloro-6-hydroxy-tetrahydroisoquinolines (1-butyl-, 1-phenyl- and 1-benzyl derivatives) were prepared to explore the influence of each of these groups at the 1-position on the affinity for dopamine receptors. All the compounds displayed affinity for D(1)-like and/or D(2)-like dopamine receptors in striatal membranes, and were unable to inhibit [(3)H]-dopamine uptake in striatal synaptosomes. Different structure requirements have been observed for adequate D(1) or D(2) affinities. This paper details the synthesis, structural elucidation, dopaminergic binding assays, structure-activity relationships (SAR) of these three series of isoquin…
Effects of 7-OH-DPAT and U 99194 on the behavioral response to hot plate test, in rats
2005
Aim of present study was to investigate in male Wistar rats, whether behavioral response to hot plate test application could be influenced by systemic administration of 7-OH-DPAT, a dopaminergic (DA) D3 versus D2 receptor agonist, or U 99194, a DA D3 versus D2 receptor antagonist. Each trial lasted no more than 10 s and the whole experimental session lasted 120 min. Animal behavior was recorded by means of a digital videocamera and later, frame by frame examined using a professional videorecorder. Latency of each behavioral pattern, characterizing the response, was analysed, showing significant changes only with U 99194. A multivariate cluster analysis indicated the presence of three main b…
In vivo imaging of dopamine receptors in a model of temporal lobe epilepsy
2010
Alterations in dopamine neurotransmission in animal models of epilepsies have been frequently demonstrated using invasive neuroscience or ex vivo techniques. We aimed to test whether corresponding alterations could be detected by noninvasive in vivo brain imaging with positron emission tomography (PET) in the chronic phase of the rat pilocarpine model of temporal lobe epilepsy.Six pilocarpine-treated Wistar rats exhibiting spontaneous recurrent seizures and nine control rats were studied with PET using [(18)F]-fallypride, a high-affinity dopamine D(2/3) receptor ligand. Parametric images of [(18)F]-fallypride specific binding were calculated using a reference tissue method, and the two grou…
Enantioselective syntheses of dopaminergic (R)- and (S)-benzyltetrahydroisoquinolines.
2001
Optically pure (1S,R)- and (1R,S)-benzyltetrahydroisoquinolines (BTHIQs), 12a,b as the major diastereomers, were prepared by stereoselective reduction of the isoquinolinium salt possessing (R)- and (S)-phenylglycinol as the chiral auxiliary, respectively. The absolute configurations of (1S,R)-13a hydrochloride (O-debenzoylated derivative from 12a) and (1R,S)-12b diastereomers were unambiguously determined by single-crystal X-ray analysis. Reductive removal of the chiral auxiliary group, subsequent N-propylation, and cleavage of the methylenedioxy group furnished the optically active catecholamines (1S)-16a and (1R)-16b in good overall yield. We have separately prepared for the first time pa…
Lunasin-induced behavioural effects in mice: Focus on the dopaminergic system
2013
The present study for the first time is devoted to identify central effects of synthetic lunasin, a 43 amino acid peptide. A markedly expressed neuroleptic/cataleptic effect was observed at low (0.1-10 nmol/mouse) centrally administered doses in male C57Bl/6 mice. Lunasin considerably reduced the amphetamine hyperlocomotion but weakly apomorphine climbing behaviour. No influence on ketamine and bicuculline effects was observed. Binding assay studies demonstrated modest affinity of lunasin for the dopamine D₁ receptor (Ki=60 ± 15 μM). In a functional assay of cAMP accumulation on live cells lunasin antagonised apomorphine effect on D₁ receptor activation (pEC₅₀=6.1 ± 0.3), but had no effect …
Dopamine-related genes and spontaneous smoking cessation in ever-heavy smokers
2011
Several studies have provided evidence for associations of polymorphisms located in and near dopamine-related genes and nicotine dependence and other smoking-related phenotypes, including pharmacogenetic interactions. Aim: The purpose of the present work was to examine the association of SNPs in the DOPA decarboxylase (DDC), dopamine receptor D2 (DRD2) and dopamine transporter (SLC6A3) genes with smoking cessation in a large retrospective study featuring approximately 900 cessation events. Materials & methods: Data originated from the enrollment questionnaire of the epidemiological ESTHER study of community-dwelling adults aged 50–74 years, conducted in the German state of Saarland bet…
Dopamine acting through D2 receptors modulates the expression of PSA-NCAM, a molecule related to neuronal structural plasticity, in the medial prefro…
2008
A "neuroplastic" hypothesis proposes that changes in neuronal structural plasticity may underlie the aetiology of depression and the action of antidepressants. The medial prefrontal cortex (mPFC) is affected by this disorder and shows an intense expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a plasticity-associated molecule, which is expressed mainly in interneurons. The monoamines serotonin, dopamine and noradrenaline are the principal targets of antidepressant action. Pharmacological manipulation of serotonin levels regulates synaptophysin and PSA-NCAM expression in the adult mPFC. However, the involvement of structural plasticity on the antidepress…
2,3,9- and 2,3,11-Trisubstituted tetrahydroprotoberberines as D2 dopaminergic ligands
2013
Dopamine-mediated neurotransmission plays an important role in relevant psychiatric and neurological disorders. Nowadays, there is an enormous interest in the development of new dopamine receptors (DR) acting drugs as potential new targets for the treatment of schizophrenia or Parkinson's disease. Previous studies have revealed that isoquinoline compounds such as tetrahydroisoquinolines (THIQs) and tetrahydroprotoberberines (THPBs) can behave as selective D-2 dopaminergic alkaloids since they share structural similarities with dopamine. In the present study we have synthesized eleven 2,3,9- and 2,3,11-trisubstituted THPB compounds (six of them are described for the first time) and evaluated…