Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Antisera Against Certain Conserved Surface-Exposed Peptides of Nontypeable Haemophilus influenzae Are Protective

We thank Timothy VanWagoner for bioinformatics support, Huda Mussa for assistance with sequencing and Brett Cole for assistance with animal studies. We thank Arnold Smith for inspiration and persistence in understanding the basic biology of H. flu..The authors gratefully acknowledge the Children’s Hospital Foundation for promoting the Department of Pediatrics Research Infrastructure. The Foundation provided no financial support for this specific project.Nontypeable Haemophilus influenzae (NTHi) cause significant disease, including otitis media in children, exacerbations of chronic obstructive pulmonary disease, and invasive disease in susceptible populations. No vaccine is currently available to prevent NTHi disease. The interactions of NTHi and the human host are primarily mediated by lipooligosaccharide and a complex array of surface-exposed proteins (SEPs) that act as receptors, sensors and secretion systems. We hypothesized that certain SEPs are present in all NTHi strains and that a subset of these may be antibody accessible and represent protective epitopes. Initially we used 15 genomic sequences available in the GenBank database along with an additional 11 genomic sequences generated by ourselves to identify the core set of putative SEPs present in all strains. Using bioinformatics, 56 core SEPs were identified. Molecular modeling generated putative structures of the SEPs from which potential surface exposed regions were defined. Synthetic peptides corresponding to ten of these highly conserved surface-exposed regions were used to raise antisera in rats. These antisera were used to assess passive protection in the infant rat model of invasive NTHi infection. Five of the antisera were protective, thus demonstrating their in vivo antibody accessibility. These five peptide regions represent potential targets for peptide vaccine candidates to protect against NTHi infection.Yeshttp://www.plosone.org/static/editorial#pee

The Battle for a Sustainable Food Supply

Since the time that Homo sapiens took up farming, a battle has been waged against pests and diseases which can cause significant losses in crop yield and threaten a sustainable food supply. Initially, early control techniques included religious practices or folk magic, hand removal of weeds and insects, and “chemical” techniques such as smokes, easily available minerals, oils and plant extracts known to have pesticidal activity. But it was not until the early twentieth century that real progress was made when a large number of compounds became available for testing as pesticides due to the upsurge in organic chemistry. The period after the 1940s saw the introduction of important families of chemicals, such as the phenoxy acid herbicides, the organochlorine insecticides and the dithiocarbamate fungicides. The introduction of new pesticides led to significant yield increases, but concern arose over their possible negative effects on human health and the environment. In time, resistance started to occur, making these pesticides less effective. This led agrochemical companies putting in place research looking for new modes of action and giving less toxic and more environmentally friendly products. These research programmes gave rise to new pesticide families, such as the sulfonylurea herbicides, the strobilurin fungicides and the neonicotinoid insecticide classes