Second, VE-822 price repeated cocaine administration induces behavioral

sensitization a form of behavioral plasticity believed to underlie certain aspects of addiction. Third, a key role for dopaminergic systems in mediating cocaine’s effects has been demonstrated through both pharmacological and genetic methods. Finally, and most importantly, unbiased genetic screens, feasible because of the simplicity and scale with which flies can be manipulated in the laboratory, have identified several novel genes and pathways whose role in cocaine behaviors had not been anticipated. Many of these genes and pathways have been validated in mammalian models of drug addiction. We focus in this review on the role of LIM-only proteins in cocaine-induced behaviors. (c) 2008 Elsevier Ltd. All rights reserved.”
“The glycoprotein complex of paramyxoviruses mediates receptor binding and membrane fusion. In particular, the measles virus (MV) fusion (F) protein executes membrane fusion, after receptor JQ-EZ-05 manufacturer binding by the hemagglutinin (H) protein. Structures and single amino acids influencing fusion function have been identified in the F-protein ectodomain and cytoplasmic

tail, but not in its transmembrane (TM) region. Since this region influences function of the envelope proteins of other viruses, we examined its role in the MV F protein. Alanine-scanning mutagenesis revealed that an F protein with a single mutation Amyloid precursor protein secretase of a central TM region leucine (L507A) was more fusogenic than the unmodified F protein while retaining similar kinetics of proteolytic processing. In contrast, substitution of residues located near the edges of the lipid bilayer reduced fusion activity. This was true not only when the mutated F proteins were coexpressed with H but also in the context of infections with recombinant viruses. Analysis of the H-F complexes with reduced fusion activities revealed that more precursor (F(0)) than activated (F(1+2)) protein coprecipitated with H. In contrast, in complexes with enhanced fusion activity, including H-F(L507A), the F(0)/F(1+2) ratio

shifted toward F(1+2). Thus, fusion activity correlated with an active F-H protein complex, and the MV F protein TM region modulated availability of this complex.”
“Dopamine neurons in the ventral tegmental area (VTA) play a very important role in a variety of physiological as well as addictive behaviors. However, a clear understanding of the cellular mechanisms underlying these behaviors is still missing. Within the VTA, recent studies have shown that forms of synaptic plasticity Such as long-term potentiation (UP) and long-term depression (LTD) are produced by drugs of abuse. The main goal of this review is to discuss the relationship between plasticity at excitatory synapses in the VTA and addiction-associated behaviors such as behavioral sensitization and cocaine self-administration.