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To identify the molecular mechanisms underlying psychostimulant-elicited plasticity in the brain reward system, we undertook a phenotype-driven approach using genome-wide microarray profiling of striatal transcripts from three genetic and one pharmacological mouse models of psychostimulant or dopamine supersensitivity. A small set of co-affected genes was(More)
Brain dopaminergic transmission is a critical component in numerous vital functions, and its dysfunction is involved in several disorders, including addiction and Parkinson's disease. Responses to dopamine are mediated via G protein-coupled dopamine receptors (D1-D5). Desensitization of G protein-coupled receptors is mediated via phosphorylation by members(More)
Dopaminergic dysregulation can cause motor dysfunction, but the mechanisms underlying dopamine-related motor disorders remain under debate. We used an inducible and reversible pharmacogenetic approach in dopamine transporter knockout mice to investigate the simultaneous activity of neuronal ensembles in the dorsolateral striatum and primary motor cortex(More)
Glutamate and glutamate receptors are well known to play a major excitatory role in the brain. Recent findings on ovarian steroids and selective estrogen receptor modulators (SERMs) activity on rat brain AMPA and NMDA receptors are reviewed. Ovarian steroid withdrawal by ovariectomy is without effect on NMDA and AMPA receptors in most brain regions, except(More)
l-3,4-dihydroxyphenylalanine methyl ester hydrochloride (l-DOPA) is the gold standard for symptomatic treatment of Parkinson's disease (PD), but long-term therapy is associated with the emergence of abnormal involuntary movements (AIMS) known as l-DOPA-induced dyskinesias (LID). The molecular changes underlying LID are not completely understood. Using the(More)
Evidence suggests the estrogens may play a role in various mental and neurodegenerative diseases. We review the evidence implicating estradiol in schizophrenia and Parkinson's disease. Epidemiologic and clinical studies on the effects of estrogens in schizophrenia are surveyed, and animal studies and in vitro models of the modulatory effects of estrogens on(More)
Structural abnormalities of the basal ganglia have been documented in several neuropsychiatric conditions associated with dysregulation of the dopamine system. However, the histological nature underlying these changes is largely unknown. Using magnetic resonance imaging at microscopic resolution (MRI, 9.4 T with 43 microm isotropic spatial resolution) and(More)
Using selective bi-directional breeding procedures, two different lines of mice were developed. The NC900 line is highly reactive and attacks their social partners without provocation, whereas aggression in NC100 animals is uncommon in social environments. The enhanced reactivity of NC900 mice suggests that emotionality may have been selected with(More)
Huntington's disease (HD) is an inherited neurodegenerative disorder caused by abnormal CAG repeat expansion in the IT15 gene encoding huntingtin protein (htt). Mutated htt is predicted to acquire toxic properties in specific brain regions. For instance, striatal neurons expressing dopamine receptors predominantly degenerate in HD patients. Although the(More)
The mammalian target of rapamycin (mTOR) kinase is a critical regulator of mRNA translation and is suspected to be involved in various long-lasting forms of synaptic and behavioral plasticity. However, its role in motor learning and control has never been examined. This study investigated, in mice, the implication of mTOR in the learning processes(More)