Neurokinin 1 receptor antagonism as a possible therapy for alcoholism

Alcohol dependence is a major public health challenge in need of new treatments. As alcoholism evolves, stress systems in the brain play an increasing role in motivating continued alcohol use and relapse. We investigated the role of the neurokinin 1 receptor (NK1R), a mediator of behavioral stress responses, in alcohol dependence and treatment. In preclinical studies, mice genetically deficient in NK1R showed a marked decrease in voluntary alcohol consumption and had an increased sensitivity to the sedative effects of alcohol. In a randomized controlled experimental study, we treated recently detoxified alcoholic inpatients with an NK1R antagonist (LY686017; n = 25) or placebo (n = 25). LY686017 suppressed spontaneous alcohol cravings, improved overall well-being, blunted cravings induced by a challenge procedure, and attenuated concomitant cortisol responses. Brain functional magnetic resonance imaging responses to affective stimuli likewise suggested beneficial LY686017 effects. Thus, as assessed by these surrogate markers of efficacy, NK1R antagonism warrants further investigation as a treatment in alcoholism.     

Explaining temporal variation in soil CO2 efflux in a mature spruce forest in Southern Germany

An open dynamic chamber system was used to measure the soil CO₂ efflux intensively and continuously throughout a growing season in a mature spruce forest (Picea abies) in Southern Germany. The resulting data set contained a large amount of temporally highly resolved information on the variation in soil CO₂ efflux together with environmental variables. Based on this background, the dependencies of the soil CO₂ efflux rate on the controlling environmental factors were analysed in-depth. Of the abiotic factors, soil temperature alone explained 72% of the variation in the efflux rate, and including soil water content (SWC) as an additional variable increased the explained variance to about 83%. Between April and December, average rates ranged from 0.43 to 5.15 μmol CO₂ m⁻² s⁻¹ (in November and July, respectively) with diurnal variations of up to 50% throughout the experiment. The variability in wind speed above the forest floor influenced the CO₂ efflux rates for measuring locations with a litter layer of relatively low bulk density (and hence relatively high proportions of pore spaces). For the temporal integration of flux rates for time scales of hours to days, however, wind velocities were of no effect, reflecting the fact that wind forcing acts on the transport, but not the production of CO₂ in the soil. The variation in both the magnitude of the basal respiration rate and the temperature sensitivity throughout the growing season was only moderate (coefficient of variation of 15 and 25%, respectively). Soil water limitation of the CO₂ production in the soil could be best explained by a reduction in the temperature-insensitive basal respiration rate, with no discernible effect on the temperature sensitivity. Using a soil CO₂ efflux model with soil temperature and SWC as driving variables, it was possible to calculate the annual soil CO₂ efflux for four consecutive years for which meteorological data were available. These simulations indicate an average efflux sum of 560 g C m⁻² yr⁻¹ (SE=22 g C m⁻² yr⁻¹). An alternative model derived from the same data but using temperature alone as a driver over-estimated the annual flux sum by about 7% and showed less inter-annual variability. Given a likely shift in precipitation patterns alongside temperature changes under projected global change scenarios, these results demonstrate the necessity to include soil moisture in models that calculate the evolution of CO₂ from temperate forest soils.