Mouse psychosocial stress reduces motivation and cognitive function in operant reward tests:A model for reward pathology with effects of agomelatine

A major domain of depression is decreased motivation for reward. Translational automated tests can be applied in humans and animals to study operant reward behaviour, aetio-pathophysiology underlying deficits therein, and effects of antidepressant treatment. Three inter-related experiments were conducted to investigate depression-relevant effects of chronic psychosocial stress on operant behaviour in mice. (A) Non-manipulated mice were trained on a complex reversal learning (CRL) test with sucrose reinforcement; relative to vehicle (VEH), acute antidepressant agomelatine (AGO, 25mg/kg p.o.) increased reversals. (B) Mice underwent chronic social defeat (CSD) or control handling (CON) on days 1-15, and were administered AGO or VEH on days 10-22. In a progressive ratio schedule motivation test for sucrose on day 15, CSD mice made fewer responses; AGO tended to reverse this effect. In a CRL test on day 22, CSD mice completed fewer reversals; AGO tended to increase reversals in CSD mice associated with an adaptive increase in perseveration. (C) Mice with continuous operant access to water and saccharin solution in the home cage were exposed to CSD or CON; CSD mice made fewer responses for saccharin and water and drank less saccharin in the active period, and drank more water in the inactive period. In a separate CSD cohort, repeated AGO was without effect on these home cage operant and consummatory changes. Overall, this study demonstrates that psychosocial stress in mice leads to depression-relevant decreases in motivation and cognition in operant reward tests; partial reversal of these deficits by AGO provides evidence for predictive validity

Is Being 'Soft on Crime' the Solution to Rising Crime Rates? Evidence from Germany

Based on a theoretical framework on informal, custodial and non-custodial sentencing, the paper provides econometric tests on the effectiveness of police, public prosecution and courts. Using a unique dataset covering German states for the period 1977- 2001, a comprehensive system of criminal prosecution indicators is derived and subsequently related to the incidence of six major offence categories using panel-econometrics. Empirical evidence suggests that the criminal policy of diversion failed as increasing shares of dismissals by prosecutors and judges enhance crime rates in Germany. Crime is significantly deterred by higher clearance and conviction rates, while the effects of indicators representing type (fine, probation, imprisonment) and severity (length of prison sentence, amount of fine) of punishment are often small and insignificant

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

Scanning Rate Extension of Conventional DSCs through Indirect Measurements

In this work, a method is presented which allows the determination of calorimetric information, and thus, information about the precipitation and dissolution behavior of aluminum alloys during heating rates that could not be previously measured. Differential scanning calorimetry (DSC) is an established method for in-situ recording of dissolution and precipitation reactions in various aluminum alloys. Diverse types of DSC devices are suitable for different ranges of scanning rates. A combination of the various available commercial devices enables heating and cooling rates from 10−4 to 5 Ks−1 to be covered. However, in some manufacturing steps of aluminum alloys, heating rates up to several 100 Ks−1 are important. Currently, conventional DSC cannot achieve these high heating rates and they are still too slow for the chip-sensor based fast scanning calorimetry. In order to fill the gap, an indirect measurement method has been developed, which allows the determination of qualitative information, regarding the precipitation state, at various points of any heat treatment. Different rapid heat treatments were carried out on samples of an alloy EN AW-6082 in a quenching dilatometer and terminated at defined temperatures. Subsequent reheating of the samples in the DSC enables analysis of the precipitation state of the heat-treated samples. This method allows for previously un-measurable heat treatments to get information about the occurring precipitation and dissolution reactions during short-term heat treatments

A Phenomenological Mechanical Material Model for Precipitation Hardening Aluminium Alloys

Age hardening aluminium alloys obtain their strength by forming precipitates. This precipitation-hardened state is often the initial condition for short-term heat treatments, like welding processes or local laser heat treatment to produce tailored heat-treated profiles (THTP). During these heat treatments, the strength-increasing precipitates are dissolved depending on the maximum temperature and the material is softened in these areas. Depending on the temperature path, the mechanical properties differ between heating and cooling at the same temperature. To model this behavior, a phenomenological material model was developed based on the dissolution characteristics and experimental flow curves were developed depending on the current temperature and the maximum temperature. The dissolution characteristics were analyzed by calorimetry. The mechanical properties at different temperatures and peak temperatures were recorded by thermomechanical analysis. The usual phase transformation equations in the Finite Element Method (FEM) code, which were developed for phase transformation in steels, were used to develop a phenomenological model for the mechanical properties as a function of the relevant heat treatment parameters. This material model was implemented for aluminium alloy 6060 T4 in the finite element software LS-DYNA (Livermore Software Technology Corporation)

Combined Calorimetry, Thermo-Mechanical Analysis and Tensile Test on Welded EN AW-6082 Joints

Wide softening zones are typical for welded joints of age hardened aluminium alloys. In this study, the microstructure evolution and distribution of mechanical properties resulting from welding processes of the aluminium alloy EN AW-6082 (AlSi1MgMn) was analysed by both in-situ and ex-situ investigations. The in-situ thermal analyses included differential scanning calorimetry (DSC), which was used to characterise the dissolution and precipitation behaviour in the heat affected zone (HAZ) of welded joints. Thermo-mechanical analysis (TMA) by means of compression tests was used to determine the mechanical properties of various states of the microstructure after the welding heat input. The necessary temperature–time courses in the HAZ for these methods were measured using thermocouples during welding. Additionally, ex-situ tensile tests were done both on specimens from the fusion zone and on welded joints, and their in-depth analysis with digital image correlation (DIC) accompanied by finite element simulations serve for the description of flow curves in different areas of the weld. The combination of these methods and the discussion of their results make an essential contribution to understand the influence of welding heat on the material properties, particularly on the softening behaviour. Furthermore, the distributed strength characteristic of the welded connections is required for an applicable estimation of the load-bearing capacity of welded aluminium structures by numerical methods

Effects of Aging under Stress on Mechanical Properties and Microstructure of EN AW 7075 Alloy

In the present study, microstructural and mechanical properties of EN AW 7075 following stress-aging were assessed. For this purpose, properties of stress-aged samples were compared with values obtained for conventionally aged counterparts. It is revealed that the strength and hardness of EN AW 7075 can be increased by the presence of external stresses during aging. Precipitation kinetics were found to be accelerated. The effects of conventional and stress-aging on the microstructure were analyzed using synergetic techniques: the differently aged samples were probed by differential scanning calorimetry (DSC) in order to characterize the precipitation processes. DSC was found to be an excellent screening tool for the analysis of precipitation processes during aging of this alloy with and without the presence of external stresses. Furthermore, using electron microscopy it was revealed that an improvement in mechanical properties can be correlated to changes in the morphologies and sizes of precipitates formed

In situ high-energy X-ray diffraction of precipitation and dissolution reactions during heating of Al alloys

During heating of Al alloys, typically a sequence of precipitation and dissolutionreactions occurs and the single (partly opposing) reactions superimpose. Differentialscanning calorimetry (DSC) is one common technique to analyse thekinetic development of precipitation and dissolution in Al alloys, but thesuperposition of the exothermic precipitation and endothermic dissolutionreactions complicates the DSC signal interpretation, as DSC measures the sum ofany heat effect. Synchrotron high-energy X-ray diffraction (HEXRD) allows thekinetic development of phase transformations to be obtained and can supportthe separation of superimposed DSC signals. HEXRD results from this workoffer a new approach to separate part of the superimposed reactions and theirkinetic development for the equilibrium phases b-Mg2Si in EN AW-6082 andg-Mg(Zn,Cu,Al)2 in EN AW-7150. Comparing DSC and HEXRD results confirmsserious overlap issues. Common DSC evaluation methods alone, usingzero crossing between endothermic and exothermic heat flow or peak positionscan be misleading regarding individual reaction start and finish temperatures aswell as regarding reaction intensities, which can be unambiguously determinedby in situ HEXRD