This review focuses on the role of insulin signaling in regulating DA homeostasis and DA signaling, and the potential impact of impaired insulin signaling in obesity and psychostimulant abuse.
This article is part of a Special Issue entitled ‘Synaptic Plasticity and Addiction’. (C) 2011 Elsevier Ltd. All rights reserved.”
“Cocaine-induced
plasticity of mesocorticolimbic dopamine (DA) neurons, originating in the ventral tegmental area (WA), persists in the absence of cocaine and may contribute to both drug-craving and relapse. Glutamate AMPA receptors click here (AMPARs) in these neurons are implicated in this plasticity. However, there is no ultrastructural evidence that the absence of cocaine following repeated administrations affects the critical surface/synaptic availability of AMPAR GluR1 subunits in either DA or non-DA, putative GABAergic neurons within the VIA. To assess this, we used electron microscopic immunolabeling in the VTA of adult male mice sacrificed at 30 min or 72 h after receiving the final of six (15 mg/kg) cocaine injections, a dosing Selleckchem FK506 paradigm that resulted in development of locomotor sensitization. At each time point, both cocaine- and saline-injected mice showed AMPAR GluR1 immunogold labeling in somatodendritic profiles, many of which contained immunoperoxidase labeling for the DA-synthesizing enzyme, tyrosine hydroxylase (TH). At 30 min after the last
injection, when cocaine was systemically present, only the non-TH labeled dendrites showed a significant increase Loperamide in the synaptic/plasmalemmal density of GluR1 immunogold particles. At 72 h, when systemic cocaine was depleted, synaptic GluR1 labeling was greatly enhanced in TH-containing dendrites throughout the VTA and in non-TH dendrites of the limbic-associated paranigral
VTA. Our results demonstrate that systemic cocaine produces GluR1 trafficking specifically in non-DA neurons of the VFA, which may subsequently contribute to the abstinent-induced enhancement of AMPA receptor synaptic transmission in mesocorticolimbic DA neurons leading to heightened drug seeking behavior.
This article is part of a Special Issue entitled ‘Synaptic Plasticity and Addiction’. (C) 2011 Elsevier Ltd. All rights reserved.”
“Background. Although physical activity has substantial health benefits and reduces mortality, few studies have examined its impact on survival beyond age 75.
Methods. Using the population-based Leisure World Cohort Study, we explored the association of activity on all-cause mortality in older adults (median age at baseline = 74 years). We followed 8,371 women and 4,828 men for 28 years or until death (median = 13 years) and calculated relative risks for various measures of activity at baseline using Cox regression analysis for four age groups (<70, 70-74, 75-79, and 80+ years) in men and women separately.
Results.