Abstract:
:The clinical efficacy of aripiprazole in the treatment of psychosis relies on a partial agonism at D2 receptors. As the expression of this receptor differs physiologically between pre- and post-synaptic sites and is affected by pathological conditions or pharmacological treatments, it appears difficult to predict the clinical response to partial agonists. In addition, the response to this novel antipsychotic was shown to depend on the cell-line and the pathway analyzed, suggesting a functional selective profile at the D2 receptor. This study aims at examining the influence of receptor density and ionic environment on the pharmacological properties of aripiprazole. A cell line was developed in which the expression of the recombinant D2 receptor can be tightly manipulated using doxycycline and sodium butyrate. The potency and efficacy of aripiprazole and other reference D2 receptor ligands were examined in [35S]GTPγS binding assays, in buffers containing either NaCl or N-methyl-D-glucamine (NMDG) which is proposed to enhance G protein coupling. Increasing the density of D2 receptors considerably enhanced the [35S]GTPγS binding induced by dopamine and the full agonist NPA. In maximally induced cells, the agonist properties of the partial agonist (-)-3-PPP was revealed in a buffer containing NaCl, whereas the response to aripiprazole was not evidenced. Substituting NMDG for NaCl promoted the response to dopamine and (-)3-PPP and was proven efficient to reveal the partial agonist profile of aripiprazole. While NMDG substitution for NaCl strongly enhanced receptor-G protein coupling, these ionic manipulations are likely to influence receptor conformations, thereby modulating the activation of signaling pathways. Our data obtained with partial agonists acting at the D2 receptor suggest that these changes in the experimental conditions could contribute to reveal the functional selective profile of GPCR ligands. They also emphasize that the properties of functional selective ligands do not only depend on receptor density but also on the surrounding environment which likely differs between brain structures.
journal_name
Prog Neuropsychopharmacol Biol Psychiatryauthors
Koener B,Focant MC,Bosier B,Maloteaux JM,Hermans Edoi
10.1016/j.pnpbp.2011.08.007subject
Has Abstractpub_date
2012-01-10 00:00:00pages
60-70issue
1eissn
0278-5846issn
1878-4216pii
S0278-5846(11)00254-5journal_volume
36pub_type
杂志文章abstract::1. The authors attempted to detect a possible effect of treatment with phenelzine on a physiological response to nicotine in the rat. 2. Positive findings in an animal model suggest the feasibility of more complicated experiments in animals and the possibility of studies involving human subjects. 3. Treatment of Sprag...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/0278-5846(93)90065-z
更新日期:1993-09-01 00:00:00
abstract::Cigarette smoking is the leading preventable cause of death in the Western world, with a considerably higher prevalence observed in schizophrenia compared to the general population. Despite the negative health consequences of smoking heavily, it has been proposed that individuals with schizophrenia may maintain smokin...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章,评审
doi:10.1016/j.pnpbp.2013.07.010
更新日期:2014-07-03 00:00:00
abstract::1. In extensively washed synaptic membrane preparations from rat prefrontal cortex, the "in vitro" addition of either the D1 (SKF 38393) or the D2 (LY 171555) specific agonists markedly decreased the apparent affinity of the NMDA receptor antagonist [3H]-MK801 specific binding. In the same membrane preparation, the co...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/0278-5846(96)00039-5
更新日期:1996-05-01 00:00:00
abstract::Antidepressant drugs and electroconvulsive seizure (ECS)-treatment, an animal model of electroconvulsive therapy, induce neurogenesis in adult rats. Stress and high levels of corticosterone (CORT) on the contrary inhibit neurogenesis. Hippocampal neurogenesis has been described to occur in an angiogenic niche where pr...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.pnpbp.2008.05.012
更新日期:2008-08-01 00:00:00
abstract::Although several recent studies have suggested that neuroinflammation plays a role in depression, both medication and neuroinflammatory preventive strategies have been poorly investigated. Recent studies have indicated that preconditioning with lipopolysaccharide (LPS) reduces the damage that occurs following ischemic...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.pnpbp.2020.109978
更新日期:2020-12-20 00:00:00
abstract::1. The effects of intravenous infusion of desipramine (1, 3, 10, and 60 mg/kg/day), amitriptyline, zimelidine, iprindole (3, 10, 30, 60, and 100 mg/kg/day each), imipramine (10, 30, and 100 mg/kg/day), or U-48753E (1, 3, 10, and 30 mg/kg/day) on the density of central beta-adrenergic receptors (beta-AR) were investiga...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/0278-5846(88)90011-5
更新日期:1988-01-01 00:00:00
abstract:OBJECTIVES:Several studies have suggested insulin resistance related to dyslipidemia and body weight in drug treated schizophrenia patients. Although, insulin resistance or impaired glucose tolerance is also reported in antipsychotic naïve schizophrenia patients, their relationship with dyslipidemic changes and body we...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.pnpbp.2010.06.011
更新日期:2010-10-01 00:00:00
abstract::In people with schizophrenia, cognitive abilities - including memory - are strongly associated with functional outcome. Long-term potentiation (LTP) is a form of neuroplasticity that is believed to be the physiological basis for memory. It has been postulated that antipsychotic medication can impair long-term potentia...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章,评审
doi:10.1016/j.pnpbp.2014.05.001
更新日期:2014-10-03 00:00:00
abstract:BACKGROUND:Abnormal vasopressin (VP) and oxytocin (OT) signaling may contribute to the altered activity of the hypothalamo-pituitary-adrenal (HPA) axis in major depression; however, the underlying mechanisms remain uncertain. This study characterized plasma levels and affinities of OT- and VP-reactive autoantibodies (a...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.pnpbp.2010.09.021
更新日期:2011-01-15 00:00:00
abstract::Little is known about biological predictors of treatment response in panic disorder. Our previous studies show that the brain-derived neurotrophic factor (BDNF) may play a role in the pathophysiology of major depressive disorders and eating disorders. Assuming that BDNF may be implicated in the putative common etiolog...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 临床试验,杂志文章
doi:10.1016/j.pnpbp.2005.04.010
更新日期:2005-06-01 00:00:00
abstract:BACKGROUND:With the increasing number and type of antidepressants available to clinicians, there is a need to better understand current prescribing practices and to what degree these practices reflect research findings. The purpose of this study was to examine prescribing practices in a sample of psychiatrists attendin...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0278-5846(01)00250-0
更新日期:2002-01-01 00:00:00
abstract:BACKGROUND:Previous studies concerning the association between the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and depression have provided inconclusive findings. A meta-analysis was therefore performed to investigate a more reliable estimate. METHODS:This meta-analysis recruited 26 publis...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章,meta分析
doi:10.1016/j.pnpbp.2013.06.015
更新日期:2013-10-01 00:00:00
abstract::Major depressive disorder (MDD) is associated with enhanced anxiety and reduced reward processing leading to impaired cognitive flexibility. These pathological changes during depression are accompanied by dysfunctional hypothalamic-pituitary-adrenal (HPA) axis and its impaired regulation by the amygdala. Notably, the ...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.pnpbp.2020.110000
更新日期:2020-12-20 00:00:00
abstract::The neurotoxicity of antipsychotic (AP) drugs seems to be linked with neurological side effects like extrapyramidal symptoms (EPS). On the other hand, neuroprotective effects can mitigate or slow the progressive degenerative structural changes in the brain leading to improved outcome of schizophrenia. First and second...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.pnpbp.2011.08.010
更新日期:2012-01-10 00:00:00
abstract::A strong positive association between depression and alcoholism is evident in epidemiological studies. Curiously, the incidence of smoking (nicotine intake) is also very high among depressed individuals. Because neuronal nicotinic receptors have been implicated in mood regulation as well as in reinforcing effects of a...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.pnpbp.2008.09.010
更新日期:2009-04-30 00:00:00
abstract::Recent case reports of postpartum psychosis are reviewed, which suggest hypotheses for the aetiology of this disease. The main themes are: The relationship to manic depression. Premenstrual relapse. Prepartum onset. Onset after miscarriage or evacuation of a trophoblastic tumour. Onset after bromocriptine treatment. A...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章,评审
doi:10.1016/0278-5846(94)90001-9
更新日期:1994-05-01 00:00:00
abstract:OBJECTIVE:Previous studies suggested likely mechanisms underlying the dysfunction of the default mode network (DMN) in schizophrenia. However, altered patterns of the intrinsic activity of the DMN in both deficit schizophrenia (DS) and non-deficit schizophrenia (NDS) patients, as well as the neurocognitive relationship...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.pnpbp.2018.10.012
更新日期:2019-03-08 00:00:00
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0278-5846(01)00276-7
更新日期:2002-02-01 00:00:00
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0278-5846(96)00083-8
更新日期:1996-08-01 00:00:00
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0278-5846(01)00271-8
更新日期:2002-04-01 00:00:00
abstract::1. The role of Gi-proteins on cataleptic responses induced by SCH23390 and haloperidol in chronic cocaine-treated mice was examined by intracerebroventricullor (i.c. v.) and intravenous (i. v.) injections of pertussis toxin (PTX), which catalyzes adenosine diphosphate (ADP)-ribosylation of Gi-proteins. 2. In animals p...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0278-5846(00)00134-2
更新日期:2000-11-01 00:00:00
abstract::Negative symptoms have been associated with structural impairment in the PFC, and hypothesized to arise from a central hypodopaminergic substrate. Corticofugal PFC neurons, which are inhibited by VTA DA innervation, exert a tonic excitatory modulation on DA activity in the NAS. Lesions of ascending DA forebrain projec...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章,评审
doi:10.1016/0278-5846(92)90102-k
更新日期:1992-01-01 00:00:00
abstract::Despite considerable efforts and successes investigating the function of the hippocampal formation in memory processes, there are still numerous elusive key issues. Some of them will be addressed in this review. We will argue that recent evidence supports hippocampal participation in several memory processes, such as ...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章,评审
doi:10.1016/s0278-5846(01)00153-1
更新日期:2001-05-01 00:00:00
abstract::Major depression is the most common mental disorder and a leading cause of years lived with disability. In addition to the burden attributed to depressive symptoms and reduced daily life functioning, people with major depression are at increased risk of premature mortality, particularly due to cardiovascular diseases....
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章,评审
doi:10.1016/j.pnpbp.2018.09.004
更新日期:2019-03-08 00:00:00
abstract::The purpose of the present study was to investigate the role of central cyclooxygenase (COX) pathways in the modulation of mechanical allodynia following compression of the left trigeminal ganglion. Experiments were carried out on male Sprague-Dawley rats mounted onto a stereotaxic frame under anesthesia. For compress...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.pnpbp.2009.02.010
更新日期:2009-06-15 00:00:00
abstract::1. Alzheimer's Disease (AD) is accompanied by a disruption in iron metabolism. There is no universally accepted method for detecting brain iron. 2. The authors have developed a novel "ratio" method which uses the red nucleus as an internal reference. We postulated that this method would improve our sensitivity in dete...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 临床试验,杂志文章
doi:10.1016/s0278-5846(97)00162-0
更新日期:1997-11-01 00:00:00
abstract::Age, haloperidol plasma levels and sex are associated with haloperidol induced motor side effects according to some lines of evidence, even though some conflicting findings mandate further research. We here report that age and sex were associated with dystonia during the early phases of treatment (p = 0.0006 and p = 0...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.pnpbp.2010.08.029
更新日期:2011-01-15 00:00:00
abstract::Ketamine hydrochloride elicits potent psychotomimetic and neurobehavioural effects which make it incompatible with driving; however, the direct effect on driving performance is yet to be assessed. Using an open label, within-subjects protocol, 15 males and 5 females (mean age = 30.8 years) were administered three fixe...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.pnpbp.2018.05.015
更新日期:2018-08-30 00:00:00
abstract::Higher risk of dementia is expected for patients with late onset depression (LOD) history. The IL-10 polymorphisms are associated with Alzheimer disease (AD). On the other hand, there is no study associating IL-10 polymorphisms to LOD. This study aimed to investigate the -1082G/A polymorphism association in LOD, AD pa...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.pnpbp.2013.07.021
更新日期:2013-12-02 00:00:00
abstract::The main goal of the present study was to evaluate binding to serotonin in the neocortex surrounding the epileptic focus of patients with mesial temporal lobe epilepsy (MTLE). Binding to 5-HT, 5-HT(1A), 5-HT(4), 5-HT(7) receptors and serotonin transporter (5-HTT) in T1-T2 gyri of 15 patients with MTLE and their correl...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.pnpbp.2007.04.014
更新日期:2007-08-15 00:00:00