These results suggest that transient activation of the ventral tegmental area mesolimbic dopamine system
triggers the expression of anxiety and aversion during withdrawal from multiple classes of abused drugs. Neuropsychopharmacology (2012) 37, 2405-2415; doi:10.1038/npp.2012.97; published online 13 June 2012″
“The species B human adenoviruses (HAdVs) infect cells upon attaching to CD46 or desmoglein 2 (DSG-2) by one or several of their 12 fiber knob trimers (FKs). To test whether DSG-2 and CD46 simultaneously serve as virus receptors for adenovirus type 3 (Ad3), we performed individual and combined CD46/DSG-2 loss-of-function studies in human lung A549 and 16HBE14o cells. Our find more results suggest that in these cells, DSG-2 functions as a major attachment receptor for Ad3, whereas CD46 exerts a minor contribution to virus attachment and uptake in the range of similar to 10%. However, in other cells the role of CD46 may be more pronounced depending on, e.g., the expression levels of the receptors. To test if avidity allows Ad3/7 to use CD46 as a receptor, we performed gain-of-function studies. The cell surface levels of ectopically expressed CD46 in CHO see more or human M010119 melanoma cells lacking DSG-2 positively correlated with Ad3/7 infections, while Ad11/35 infections depended on CD46 but less on
CD46 levels. Antibody-cross-linked soluble CD46 blocked Ad3/7/11/35 infections, while soluble CD46 alone blocked Ad11/35 but not Ad3/7. Soluble Ad3/7-FKs poorly inhibited Ad3/7 infection of CHO-CD46 cells, illustrating that Ad3/7-FKs bind with low affinity to CD46. This was confirmed by Biacore studies. Ad3/7-FK binding to immobilized CD46 at low density was not detected, unlike that of Ad11/35-FK. PCI-32765 price At higher CD46 densities, however, Ad3/7-FK bound to CD46 with only 15-fold-higher dissociation constants than those of Ad11/35-FK. These data show that an avidity mechanism for Ad3/7 binding to CD46 leads to infection of CD46-positive cells.”
“In humans, mu opioid-cocaine combinations (speedballs) have been reported to heighten pleasurable effects and result in greater abuse potential compared to either drug individually. Emerging evidence in
animals suggests that the ability of mu opioids to enhance the reinforcing effects of cocaine might be independent of their mu intrinsic efficacy even though mu agonist efficacy appears to be a determinant in the reinforcing effects of mu opioids themselves.
This study examined the relationship between agonist efficacy, self-administration, and the enhancement of cocaine self-administration using the high-efficacy mu agonist etonitazene.
Rhesus monkeys self-administered cocaine, heroin, etonitazene, and opioid-cocaine combinations under a progressive-ratio schedule of intravenous drug injection.
Unlike cocaine and heroin, etonitazene did not maintain consistent self-administration at any dose tested (0.001-1.0 mu g/kg/injection). However, combining etonitazene (0.1-1.