European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
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Eur Neuropsychopharmacol · Oct 2013
Vulnerability versus resilience to prenatal stress in male and female rats; implications from gene expression profiles in the hippocampus and frontal cortex.
Adverse life events during pregnancy may impact upon the developing fetus, predisposing prenatally stressed offspring to the development of psychopathology. In the present study, we examined the effects of prenatal restraint stress (PS) on anxiety- and depression-related behavior in both male and female adult Sprague-Dawley rats. In addition, gene expression profiles within the hippocampus and frontal cortex (FC) were examined in order to gain more insight into the molecular mechanisms that mediate the behavioral effects of PS exposure. ⋯ Further, the data indicated that epigenetic regulation is affected differentially in male and female PS offspring. These sex-specific alterations may, at least in part, explain the behavioral differences observed between both sexes, i.e. relative vulnerability versus resilience to PS in male versus female rats, respectively. These data reveal novel potential targets for antidepressant and mood stabilizing drug treatments including PDE inhibitors and histone deacetylase (HDAC) inhibitors.
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Eur Neuropsychopharmacol · Oct 2013
Footshock-induced responses in ventral subiculum neurons are mediated by locus coeruleus noradrenergic afferents.
The ventral subiculum (vSub) of the hippocampus is critically involved in mediating the forebrain's response to stress, particularly with regard to psychogenic stressors. Stress, in turn, is known to aggravate many psychiatric conditions including schizophrenia, depression, anxiety, and drug abuse. Pathological alterations in hippocampal function have been identified in all these disorders; thus, it is of interest to understand how stress affects this brain region. ⋯ These results suggest that the LC NE system plays an important role in mediating stress responses in the vSub. Footshock evokes both inhibition and excitation in the vSub, by activating noradrenergic inputs from the LC. These responses may contribute to stress adaptation; while an imbalance of this system may lead to pathological stress responses in mental disorders.
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Eur Neuropsychopharmacol · Oct 2013
Three-way interaction effect of 5-HTTLPR, BDNF Val66Met, and childhood adversity on depression: a replication study.
Both the serotonin transporter linked promoter region (5-HTTLPR) and the brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms have been shown to interact with unfavourable environment in relation to depression symptoms and to depression diagnosis. Several attempts have been made to study a three-way interaction effect of these factors on depression, however with contradictory results. We aimed to test the hypothesis of a three-way interaction effect and to attempt at replication in an independent population-based sample. ⋯ This three-way effect was more pronounced among girls. The current study, with a virtually similar set-up compared to previous studies, can partially confirm previous findings and their generalizability. The study also shows the importance of genetic plasticity in individuals with different environmental exposure, for different phenotypic expression.
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Eur Neuropsychopharmacol · Oct 2013
Haloperidol modulates midbrain-prefrontal functional connectivity in the rat brain.
Dopamine D₂ receptor antagonists effectively reduce positive symptoms in schizophrenia, implicating abnormal dopaminergic neurotransmission as an underlying mechanism of psychosis. Despite the well-established, albeit incomplete, clinical efficacies of D₂ antagonists, no studies have examined their effects on functional interaction between brain regions. We hypothesized that haloperidol, a widely used antipsychotic and D₂ antagonist, would modulate functional connectivity in dopaminergic circuits. ⋯ Haloperidol induced focal changes in functional connectivity were found to be the most strongly associated with ascending dopamine projections. These included reduced connectivity between the midbrain and the medial prefrontal cortex and hippocampus, possibly relating to its therapeutic action, and decreased coupling between substantia nigra and motor areas, which may reflect dyskinetic effects. These data may help in further characterizing the functional circuits modulated by antipsychotics that could be targeted by innovative drug treatments.