European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
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Eur Neuropsychopharmacol · Dec 2015
Effects of haloperidol and aripiprazole on the human mesolimbic motivational system: A pharmacological fMRI study.
The atypical antipsychotic drug aripiprazole is a partial dopamine (DA) D2 receptor agonist, which differentiates it from most other antipsychotics. This study compares the brain activation characteristic produced by aripiprazole with that of haloperidol, a typical D2 receptor antagonist. Healthy participants received an acute oral dose of haloperidol, aripiprazole or placebo, and then performed an active aversive conditioning task with aversive and neutral events presented as sounds, while blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was carried out. ⋯ Accordingly, the task-related BOLD-fMRI response in the mesolimbic motivational system was diminished in the haloperidol group compared to the placebo group, particularly in the ventral striatum, whereas the aripiprazole group showed task-related activations intermediate of the placebo and haloperidol groups. The current results show differential effects on brain function by aripiprazole and haloperidol, probably related to altered DA transmission. This supports the use of pharmacological fMRI to study antipsychotic properties in humans.
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Eur Neuropsychopharmacol · Dec 2015
Alterations in brain-derived neurotrophic factor (BDNF) and its precursor proBDNF in the brain regions of a learned helplessness rat model and the antidepressant effects of a TrkB agonist and antagonist.
Role of brain-derived neurotrophic factor (BDNF)-TrkB signaling in a learned helplessness (LH) model of depression was investigated. LH rats showed a reduction of BDNF in the medial prefrontal cortex (mPFC), CA3, and dentate gyrus (DG) of the hippocampus, whereas LH rats showed an increase in BDNF in the nucleus accumbens (NAc). Furthermore, levels of proBDNF, a BDNF precursor, were higher in the mPFC, but lower in the NAc, of LH rats. ⋯ Additionally, ANA-12 (0.5mg/kg, i.p.) significantly improved an increased phosphorylation of TrkB in the NAc of LH rats. In conclusion, these results suggest that LH causes depression-like behavior by altering BDNF in the brain regions, and that proBDNF-BDNF processing and transport may be altered in the mPFC-NAc circuit of LH rats. Therefore, TrkB agonists might exert antidepressant effects by stimulating TrkB in the IL, CA3, and DG, while TrkB antagonists might exert antidepressant effects by blocking TrkB in the NAc.
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Eur Neuropsychopharmacol · Dec 2015
Anterior cingulate Glutamate-Glutamine cycle metabolites are altered in euthymic bipolar I disorder.
Bipolar disorder (BD) has been consistently associated with abnormalities in the Glutamate/GABA-Glutamine cycle. Magnetic resonance spectroscopy (MRS) studies have reported increased brain Glutamate (Glu) and Glx (Glu+Glutamine) in subjects with BD. However, data on separate measures of GABA and Glutamine (Gln) in BD are sparse due to overlapping resonant signals. ⋯ Neither lithium nor antipsychotic use influenced metabolite levels. The ACC MRS findings indicate that the glutamatergic function in euthymic medicated BD patients is altered relative to controls. Whether this feature is a metabolic signature of euthymic BD subjects should be the focus of future studies.