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O Guillin

Publications and source records attributed to O Guillin.

8 recordsLinked to original sources
PubMed2006

The dopamine D3 receptor: a therapeutic target for the treatment of neuropsychiatric disorders.

The role of the D(3) receptor has remained largely elusive before the development of selective research tools, such as selective radioligands, antibodies, various highly specific pharmacological agents and knock-out mice. The data collected so far with these tools have removed some of the uncertainties regarding the functions mediated by the D(3) receptor. The D(3) receptor is an autoreceptor that controls the phasic, but not tonic activity of dopamine neurons. The D(3) receptor, via regulation of its expression by the brain-derived neurotrophic factor (BDNF), mediates sensitization to dopamine indirect agonists. This process seems responsible for side-effects of levodopa (dyskinesia) in the treatment of Parkinson's disease (PD), as well as for some aspects of conditioning to drugs of abuse. The D(3) receptor mediates behavioral abnormalities elicited by glutamate/NMDA receptor blockade, which suggests D(3) receptor-selective antagonists as novel antipsychotic drugs. These data allow us to propose novel treatment options in PD, schizophrenia and drug addiction, which are awaiting evaluation in clinical trials.

Animals↗
PubMed2001

BDNF controls dopamine D3 receptor expression and triggers behavioural sensitization.

Brain-derived neurotrophic factor (BDNF), like other neurotrophins, is a polypeptidic factor initially regarded to be responsible for neuron proliferation, differentiation and survival, through its uptake at nerve terminals and retrograde transport to the cell body. A more diverse role for BDNF has emerged progressively from observations showing that it is also transported anterogradely, is released on neuron depolarization, and triggers rapid intracellular signals and action potentials in central neurons. Here we report that BDNF elicits long-term neuronal adaptations by controlling the responsiveness of its target neurons to the important neurotransmitter, dopamine. Using lesions and gene-targeted mice lacking BDNF, we show that BDNF from dopamine neurons is responsible for inducing normal expression of the dopamine D3 receptor in nucleus accumbens both during development and in adulthood. BDNF from corticostriatal neurons also induces behavioural sensitization, by triggering overexpression of the D3 receptor in striatum of hemiparkinsonian rats. Our results suggest that BDNF may be an important determinant of pathophysiological conditions such as drug addiction, schizophrenia or Parkinson's disease, in which D3 receptor expression is abnormal.

Animals↗
PubMed2000

Brain derived neurotrophic factor (BDNF) gene variants association with age at onset and therapeutic response in schizophrenia.

Schizophrenia is a heterogeneous disease involving genetic and environmental factors. The frequency of structural brain abnormalities or physical anomalies supports a neurodevelopmental etiology, especially in early onset schizophrenia. Brain-Derived-Neurotrophic-Factor (BDNF) is involved in the neurodevelopment of dopaminergic (DA)-related systems and interacts with the meso-limbic DA systems, involved in the therapeutic response to antipsychotic drugs and substance abuse. In addition, BDNF promotes and maintains dopamine D3 receptor (DRD3) expression. In a French Caucasian population, we found no statistical difference in allele or genotype distribution of the BDNF gene dinucleotide repeat polymorphism (166-174 bp) between the whole group of schizophrenic patients and controls. By contrast, an excess of the 172-176 bp alleles was found in patients with late onset, in neuroleptic-responding patients and in non-substance-abusing patients. BDNF gene variants thus appear to be associated with developmental features of schizophrenia. In addition, this association with good treatment responding was independent from the association found with the DRD3 Ball gene polymorphism in the same population. These results suggest an independent contribution of each gene to a treatment-sensitive form of schizophrenia.

Adult↗
PubMedDate not supplied

[Validation of the French translation and factorial structure of the Tiffany and Drobes Smoking Urge Questionnaire].

UNLABELLED: Over the past 10 years researches and clinicians have made substantial progress in understanding and treating nicotine dependence. To demonstrate the effectiveness of these treatments, reliable and sensitive measures of change and outcome must be used. In the nicotine dependence treatment literature numerous outcome have been used: frequencies drug use, problems associated with substance use, psychiatric comorbidity, withdrawal severity, and craving. The term craving reflects the subjective reports of addicts regarding their attempts to abstain from drug use and the state of their minds at the point at which they attempt to fail. Exposure to cues previously associated with nicotine play a role in precipitating relapse in eliciting a conditioned craving/withdrawal response and can be measures by the Questionnaire of Smoking Urge (QSU). OBJECTIVE OF THE STUDY: Validation in a French translated version of the QSU published in 1991 by Tiffany and Drobes. METHODOLOGY: 42 male and 62 female participated in the study with the translated questionnaire: mean age was 36.7 years, mean age at starting and mean duration of tobacco consumption was respectively 20.2 years old and 16.5 years, daily consumption was 16.6 cigarettes per day. The French translation of the QSU was administered to smokers instructed to abstain from smoking one hour and a half to three hours. RESULTS: The back translation has been accepted by Tiffany because more than 85% of the items are similar to the original questionnaire. We founded the same factor analysis with two factors, "desire to smoke" and "intention to smoke" accounting for 34% and 11% of the items variance, respectively. These two factors were the same than those of the original questionnaire. CONCLUSION: The validation of the French translation of the QSU gives the opportunity to use a sensitive instrument to assess craving.

Adolescent↗
PubMedDate not supplied

[Confusion and delusions occurring during interferon-alpha treatment].

A number of side effects occurring during IFN therapy have been described. Psychiatric side effects include cognitive, behavioural and affective changes, confusion and, less commonly, psychotic symptoms. We report the case of a 52-year-old patient who had been treated for almost three years with IFN alpha for a chronic myelogenous leukemia and who presented an acute confusional episode with delusions, following the reintroduction of IFN alpha after a therapy suspension of 2 weeks. Clinical improvement occurred quite rapidly after cessation of the IFN treatment; this evolution and the normality of the biological tests, EEG and cerebral imagery suggest a causal relationship between this treatment and the psychiatric symptoms.

Confusion↗