Biological psychiatry
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Biological psychiatry · Dec 2008
Delta FosB-mediated alterations in dopamine signaling are normalized by a palatable high-fat diet.
Sensitivity to reward has been implicated as a predisposing factor for behaviors related to drug abuse as well as overeating. However, the underlying mechanisms contributing to reward sensitivity are unknown. We hypothesized that a dysregulation in dopamine signaling might be an underlying cause of heightened reward sensitivity whereby rewarding stimuli could act to normalize the system. ⋯ These results establish an underlying sensitivity to changes in reward related to dysregulation of Delta FosB and dopamine signaling that can be normalized with palatable diets and may be a predisposing phenotype in some forms of obesity.
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Biological psychiatry · Dec 2008
Varied access to intravenous methamphetamine self-administration differentially alters adult hippocampal neurogenesis.
Chronic abuse of methamphetamine produces deficits in hippocampal function, perhaps by altering hippocampal neurogenesis and plasticity. We examined how intravenous methamphetamine self-administration modulates active division, proliferation of late progenitors, differentiation, maturation, survival, and mature phenotype of hippocampal subgranular zone (SGZ) progenitors. ⋯ Intermittent (occasional access) and daily (limited and extended access) self-administration of methamphetamine impact different aspects of neurogenesis, the former producing initial pro-proliferative effects and the latter producing downregulating effects. These findings suggest that altered hippocampal integrity by even modest doses of methamphetamine could account for pronounced pathology linked to methamphetamine abuse.