River histories : A thematic review

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Modulation of anxiety by acute blockade and genetic deletion of the CB(1) cannabinoid receptor in mice together with biogenic amine changes in the forebrain.

The CB(1) cannabinoid receptor has been implicated in the control of fear and anxiety. We investigated the effects of genetic and pharmacological blockade of the CB(1) cannabinoid receptor on the behaviour of CD1 mice using three different ethological models of fear and anxiety (elevated T-maze and plus-maze and open field test of emotionality). Furthermore, we measured tissue levels of noradrenalin (NA), dopamine (DA), serotonin (5-HT) and their metabolites in several forebrain regions, i.e. prefrontal cortex, hippocampus, septum, dorsal and ventral striatum to examine the relationship between CB(1) receptor manipulation and monoaminergic neurotransmission. The major findings can be summarized as follows: the CB(1) receptor antagonist SR141617A (rimonabant) modulated anxiety in a dose-dependent manner. At a dose of 3 mg/kg i.p. the compound consistently increased anxiety parameters in all of the three different anxiety tests applied, while a lower dosage of 1mg/kg had no such effect. The neurochemical evaluation of the mice administered 3mg/kg SR141617A revealed increases in the concentrations of DOPAC and 5-HIAA in the dorsal striatum, elevated DA levels in the hippocampus and reduced dopamine turnover in the septum. Furthermore, these animals had a higher HVA/DA turnover in the frontal cortex. CB(1) receptor knockout mice as well as mice treated with the selective CB(1) receptor antagonist AM251 (3 mg/kg; i.p.) did not display any significant alterations in anxiety-related behaviour as measured with the elevated plus-maze and open field test of emotionality, respectively. Our findings support the general idea of a SR141617A-sensitive receptive site that is different from the 'classical' CB(1) receptor and that has a pivotal role in the regulation of different psychological functions. However, with regard to its functional significance in terms of anxiety our findings suggest that under physiological conditions this receptive site seems to be involved in the control of anxiolysis rather than anxiogenesis as suggested previously.Journal Articleinfo:eu-repo/semantics/publishe

Moment-preserving and mesh-adaptive reweighting method for rare-event sampling in Monte-Carlo algorithms

| openaire: EC/H2020/633053/EU//EUROfusionWe present novel roulette schemes for rare-event sampling that are both structure-preserving and unbiased. The boundaries where Monte Carlo markers are split and deleted are placed automatically and adapted during runtime. Extending existing codes with the new schemes is possible without severe changes because the equation of motion for the markers is not altered. These schemes can also be applied in the presence of nonlinear and nonlocal coupling between markers. As an illustrative application, we have implemented this method in the ASCOT-RFOF code, used to simulate fast-ion generation by radio-frequency waves in fusion plasmas. In this application, with this method the Monte-Carlo noise level for typical fast-ion energies can be reduced at least of one order of magnitude without increasing the computational effort.Peer reviewe