Abstract:
BACKGROUND:Knockout (KO) mice invalidated for the dopamine transporter (DAT) constitute a powerful animal model of neurobiological alterations associated with hyperdopaminergia relevant to schizophrenia and attention-deficit/hyperactivity disorder (ADHD). METHODS:Because of continuously increasing evidence for a neuromodulatory role of endocannabinoids in dopamine-related pathophysiological responses, we assessed endocannabinoid signaling in DAT KO mice and evaluated the ability of endocannabinoid ligands to normalize behavioral deficits, namely spontaneous hyperlocomotion in these mice. RESULTS:In DAT KO mice, we found markedly reduced anandamide levels, specifically in striatum, the dopamine nerve terminal region. Furthermore, three distinct indirect endocannabinoid agonists, the selective anandamide reuptake inhibitors AM404 and VDM11 and the fatty acid amidohydrolase inhibitor AA5HT, attenuated spontaneous hyperlocomotion in DAT KO mice. The hypolocomotor effects of AM404, VDM11, and AA5HT were significantly attenuated by co-administration of the transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine but not the selective cannabinoid type 1 (CB1)receptor antagonist AM251. Interestingly, TRPV1 binding was increased in the striatum of DAT KO mice, while CB1 receptor binding was unaffected. CONCLUSIONS:These data indicate a dysregulated striatal endocannabinoid neurotransmission associated with hyperdopaminergic state. Restoring endocannabinoid homeostasis in active synapses might constitute an alternative therapeutic strategy for disorders associated with hyperdopaminergia. In this process, TRPV1 receptors seem to play a key role and represent a novel promising pharmacological target.
journal_name
Biol Psychiatryjournal_title
Biological psychiatryauthors
Tzavara ET,Li DL,Moutsimilli L,Bisogno T,Di Marzo V,Phebus LA,Nomikos GG,Giros Bdoi
10.1016/j.biopsych.2005.08.019subject
Has Abstractpub_date
2006-03-15 00:00:00pages
508-15issue
6eissn
0006-3223issn
1873-2402pii
S0006-3223(05)01008-5journal_volume
59pub_type
杂志文章abstract:BACKGROUND:Dopamine D4 receptor (DRD4) gene polymorphisms are associated with various pharmacologic activities. This study investigated whether polymorphisms of 48-bp tandem repeats in the exon 3 of the DRD4 gene are related to neuroleptic response. METHODS:The neuroleptic response at the acute stage of schizophrenia ...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章
doi:10.1016/s0006-3223(98)00134-6
更新日期:1998-09-15 00:00:00
abstract::The effect of nortriptyline was assessed on the EEG sleep of 20 inpatients with major depressive syndrome. While 25 mg of nortriptyline had an immediate effect on REM sleep variables, relatively little influence on sleep continuity measures was noted. Subsequent administration of 75 and 100 mg of nortriptyline produce...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:
更新日期:1982-05-01 00:00:00
abstract:BACKGROUND:High rates of comorbidity, shared risk, and overlapping therapeutic mechanisms have led psychopathology research toward transdiagnostic dimensional investigations of clustered symptoms. One influential framework accounts for these transdiagnostic phenomena through a single general factor, sometimes referred ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2018.03.012
更新日期:2018-09-15 00:00:00
abstract::Intracerebroventricular (icv) administration of corticotropin-releasing hormone (CRH) or exposure to a restraint stressor causes acute anorexia in rats. However, the effects on food intake of repeated injections of CRH or repeated exposures to restraint stress have not been previously reported. As the effects of these...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(90)90046-5
更新日期:1990-05-15 00:00:00
abstract:BACKGROUND:The etiology of dementia that occurs in patients with schizophrenia is not well understood. Nicotinic acetylcholine receptors have been implicated in cognitive function, and deficits in these receptors have been reported in schizophrenia. METHODS:The present study investigates possible associations of nicot...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(03)00348-2
更新日期:2003-12-01 00:00:00
abstract::There is substantial evidence that depression is a risk factor for cardiac morbidity and mortality, both for patients without clinical evidence of coronary heart disease at index examination and for patients with established coronary disease. The relationship is most apparent for patients with a recent acute myocardia...
journal_title:Biological psychiatry
pub_type: 杂志文章,评审
doi:10.1016/s0006-3223(03)00111-2
更新日期:2003-08-01 00:00:00
abstract:BACKGROUND:Chronic stress exposure causes neuronal atrophy and synaptic deficits in the medial prefrontal cortex (PFC), contributing to development of anxiety- and depressive-like behaviors. Concomitantly, microglia in the PFC undergo morphological and functional changes following stress exposure, suggesting that micro...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2017.05.026
更新日期:2018-01-01 00:00:00
abstract::The growth hormone (GH) response to GH-releasing hormone (GHRH) is characteristically exaggerated in anorexia nervosa (AN). Hyperglycemia suppresses the GH response to GHRH in normal subjects. To test whether this inhibitory action of hyperglycemia is preserved in AN, we performed a GHRH (GHRH 1-40, 1 micrograms/kg) t...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(90)90651-h
更新日期:1990-01-15 00:00:00
abstract:BACKGROUND:The single most important risk factor for Alzheimer's pathology is age. Elderly individuals are also at increased risk for suicide, but comprehensive studies of the association between Alzheimer's pathology and suicide are lacking. We designed the current study to determine if Alzheimer's disease changes are...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(00)00952-5
更新日期:2001-01-15 00:00:00
abstract:BACKGROUND:Suvorexant is an orexin receptor antagonist for treatment of insomnia. We report results from two pivotal phase 3 trials. METHODS:Two randomized, double-blind, placebo-controlled, parallel-group, 3-month trials in nonelderly (18-64 years) and elderly (≥65 years) patients with insomnia. Suvorexant doses of 4...
journal_title:Biological psychiatry
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.biopsych.2014.10.003
更新日期:2016-01-15 00:00:00
abstract::The total number of neurons was estimated in eight brains from chronic schizophrenic men and compared with 16 gender- and age-matched controls. The average total neocortical nerve cell number was 22.12.10(9) in schizophrenics and 22.06.10(9) in controls. The estimate of total cell numbers can not demonstrate more subt...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(93)90065-l
更新日期:1993-12-01 00:00:00
abstract:BACKGROUND:Currently, no pharmacological treatments for bipolar depression exist that exert rapid (within hours) antidepressant or antisuicidal effects. We previously reported that intravenous administration of the N-methyl-D-aspartate antagonist ketamine produced rapid antidepressant effects in patients with treatment...
journal_title:Biological psychiatry
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.biopsych.2011.12.010
更新日期:2012-06-01 00:00:00
abstract:BACKGROUND:The hippocampus is likely involved in mood disorders, but in vivo evidence for the role of anatomically distinct hippocampal subregions is lacking. Multiple sclerosis, an inflammatory disease of the central nervous system, is linked to a high prevalence of depression as well as hippocampal damage and may thu...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2010.04.025
更新日期:2010-09-15 00:00:00
abstract:BACKGROUND:Cortical glutamate levels are elevated in bipolar disorder, but the interpretation of this increase is unclear because glutamate has metabolic as well as neurotransmitter roles. We investigated this by measuring vesicular glutamate transporter 1 (VGluT1) expression, which reflects activity at glutamate synap...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2009.12.004
更新日期:2010-06-01 00:00:00
abstract::Hypertonic hemolysis was increased in patients with a manic episode (n = 6, mean NaCl concentration in mol/L at which 50% of the erythrocytes was hemolyzed (H50) 3.24 +/- 0.10), compared to healthy controls (n = 12, mean H50 3.43 +/- 0.13) (p < or = 0.02) and patients with a nonaffective psychotic disorder (n = 15, me...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(95)00106-9
更新日期:1996-01-01 00:00:00
abstract::Urinary MHPG concentrations and platelet 3H-imipramine binding (Bmax, Kd) were measured in 20 psychiatric inpatients with diagnoses of major depressive disorder. Clinical assessments were performed using the Present State Examination (PSE) interview, and several dimensions of symptomatology were constructed on the bas...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(88)90003-0
更新日期:1988-03-15 00:00:00
abstract:BACKGROUND:Major depressive disorder (MDD) in the adolescent demonstrates a unique clinical profile, and pathogenic serotonergic dysregulation is hypothesized. Parenteral clomipramine (CMI) is known to distinguish adult MDD from control, but neurochallenge data are lacking in adolescent MDD. METHODS:Thirteen drug-free...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章
doi:10.1016/s0006-3223(97)00447-2
更新日期:1998-10-01 00:00:00
abstract:BACKGROUND:Cannabis use is associated with an increased risk of psychosis. One study has suggested that genetic variation in the AKT1 gene might influence this effect. METHODS:In a case-control study of 489 first-episode psychosis patients and 278 control subjects, we investigated the interaction between variation at ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2012.06.020
更新日期:2012-11-15 00:00:00
abstract::Acetylcholinesterase (AChE) from erythrocytes was solubilized by Triton X-100. Size and charge heterogeneity of AChE was investigated by polyacrylamide gel electrophoresis (PAGE) and isoelectric focusing (IEF) in polyacrylamide gels in the presence of 0.5% (v/v) Triton X-100. There were no interindividual differences ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(87)90052-7
更新日期:1987-09-01 00:00:00
abstract:BACKGROUND:GPR88 is an orphan G protein coupled receptor highly enriched in the striatum, and previous studies have focused on GPR88 function in striatal physiology. The receptor is also expressed in other brain areas, and here we examined whether GPR88 function extends beyond striatal-mediated responses. METHODS:We c...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2015.05.020
更新日期:2016-06-01 00:00:00
abstract:BACKGROUND:The reported inverse relationship between indices of central serotonin (5-HT) function and indices of impulsive aggression in human subjects suggests the possibility that enhancement of 5-HT activity will reduce impulsive aggressive behavior. Although evidence for this hypothesis is emerging, the relationshi...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/S0006-3223(97)00309-0
更新日期:1997-10-01 00:00:00
abstract:BACKGROUND:There is increasing evidence for an association between alterations of brain glutamatergic neurotransmission and the pathophysiology of affective disorders. METHODS:We studied the association between cerebrospinal fluid (CSF) metabolites, including glutamine, in unipolar and bipolar depressed patients versu...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(99)00284-x
更新日期:2000-04-01 00:00:00
abstract::Sixty-five cocaine-dependent subjects were enrolled into a 10-week randomized, double-blind study to determine the safety and efficacy of the serotonin-2 receptor antagonist, ritanserin (10 mg/day), in reducing cocaine consumption and craving. All subjects also participated in a structured intensive outpatient psychos...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/S0006-3223(96)00490-8
更新日期:1997-11-15 00:00:00
abstract::Tourette syndrome (TS) is thought to involve dopaminergic disturbances, but the nature of those disturbances remains controversial. Existing hypotheses suggest that TS involves 1) supersensitive dopamine receptors, 2) overactive dopamine transporters that cause low tonic but high phasic dopamine, 3) presynaptic dysfun...
journal_title:Biological psychiatry
pub_type: 杂志文章,评审
doi:10.1016/j.biopsych.2018.02.1172
更新日期:2018-09-01 00:00:00
abstract:BACKGROUND:Addiction relies on persistent alterations of neuronal properties, which depends on gene regulation. Activity-regulated cytoskeleton-associated protein (Arc) is an immediate early gene that modulates neuronal plasticity underlying learning and memory. Its role in cocaine-induced neuronal and behavioral adapt...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2016.05.025
更新日期:2017-04-01 00:00:00
abstract::It has previously been demonstrated that direct opiate infusion into nucleus accumbens elicits psychomotor activation in rats. In the present study, the effects of chronic treatment with five different neuroleptics on this behavioral response were investigated. All neuroleptics tested (haloperidol, sulpiride, flupenti...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(86)90006-5
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND:Considering the magnitude of the reported changes in brain volume over time in first-episode patients it is unlikely that these changes are constant over the life-span of the schizophrenic illness. Thus, one would expect the progression in brain volume change in schizophrenia to follow a more complex traject...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2007.01.004
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:A large number of studies suggest the presence of deficits in dorsolateral prefrontal cortex function during performance of working memory tasks in individuals with schizophrenia. However, working memory deficits may also present in other psychiatric disorders, such as major depression. It is not clear wheth...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(02)01674-8
更新日期:2003-03-01 00:00:00
abstract:BACKGROUND:Transcranial magnetic stimulation is a novel, experimental procedure in the treatment of psychiatric disorders, most notably mood disorders. Transcranial magnetic stimulation is currently being widely studied in other applications, and its efficacies and potential side effects are being investigated. METHOD...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(00)01086-6
更新日期:2001-03-01 00:00:00
abstract::Previous studies have demonstrated blunted beta-adrenergic responsivity in leukocytes from depressed patients. We sought to determine if this blunted cyclic adenosine monophosphate (AMP) response is specific for beta-adrenergic receptors (homologous), or whether other adenylyl cyclase-coupled receptors are also involv...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/S0006-3223(97)00154-6
更新日期:1997-11-15 00:00:00