125 or 0.25 mg/kg, i.p.). Mice injected with SB 222200 had significantly enhanced hyperactivity when challenged with cocaine or a low dose of SKF 82958 (0.125 mg/kg, i.p.) compared to control mice. Brains of mice administered vehicle or SB 222200 for 5 days were harvested after a 7-day drug-free period for dopamine D1 receptor quantification by radioligand binding. [(3)H] SCH 23390 homogenate binding studies showed a 19.7% increase in dopamine D1 receptor density in the striatum of SB 222200 treated mice. These data suggest that repeated blockade of NK-3 receptors enhances subsequent dopamine-mediated behaviors

possibly resulting from dopamine D1 receptor up-regulation in the striatum. (C) 2009 Elsevier Ltd. All rights reserved.”
“Geminiviruses selleck replicate single-stranded DNA genomes through double-stranded intermediates that associate with cellular histone proteins. Unlike RNA viruses, they are subject to RNA-directed methylation pathways that target viral chromatin and likely lead to transcriptional

gene silencing (TGS). Here we present evidence that the related geminivirus proteins AL2 and L2 are able to suppress this aspect of host defense. AL2 and L2 interact with and inactivate adenosine AZD1080 molecular weight kinase (ADK), which is required for efficient production of S-adenosyl methionine, an essential methyltransferase cofactor. We demonstrate that the viral proteins can reverse TGS of a green fluorescent protein (GFP) transgene in Nicotiana

benthamiana when overexpressed from a Potato virus X vector and that reversal of TGS by geminiviruses check details requires L2 function. We also show that AL2 and L2 cause ectopic expression of endogenous Arabidopsis thaliana loci silenced by methylation in a manner that correlates with ADK inhibition. However, at one exceptional locus, ADK inhibition was insufficient and TGS reversal required the transcriptional activation domain of AL2. Using restriction-sensitive PCR and bisulfite sequencing, we showed that AL2-mediated TGS suppression is accompanied by reduced cytosine methylation. Finally, using a methylation-sensitive single-nucleotide extension assay, we showed that transgenic expression of AL2 or L2 causes global reduction in cytosine methylation. Our results provide further evidence that viral chromatin methylation is an important host defense and allow us to propose that as a countermeasure, geminivirus proteins reverse TGS by nonspecifically inhibiting cellular transmethylation reactions. To our knowledge, this is the first report that viral proteins can inhibit TGS.”
“Introduction: Alcohol and nicotine both alter learning, locomotion, and anxiety, yet no study has directly examined the interactive effects of these drugs across these behaviors within subjects. Such a comparison would determine if the drugs produce independent effects on each behavior.