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

Feasibility study for an edge main ion charge exchange recombination spectroscopy system at ASDEX Upgrade

A feasibility study for a new edge main ion charge exchange recombination spectroscopy (CXRS) system at the ASDEX Upgrade tokamak has been carried out. This diagnostic uses the new edge fast-ion Dα (FIDA) spectrometers and the optical heads of the existing edge CXRS systems. Standard CXRS resolved temperature and rotation profiles rely on the observation of impurity emission lines. The complexity of the photoemission processes and the fact that the measured ions represent the majority bulk plasma ions (here deuterium) make the interpretation of the main ion spectra in comparison more challenging. At the plasma edge, the diagnostic capabilities in terms of temporal and spatial resolution are extremely demanding. The difficulties in the interpretation of the main ion spectra are overcome by comprehensive fitting and forward modelling of the beam halo (which introduces a major challenge) using a collisional radiative model, as described in [1]. In this work, the diagnostic set up and the sensitivity of the main ion spectra to changes in plasma parameters have been characterized. The tools and techniques necessary for a correct interpretation of the spectra are also discussed. In addition to the halo effect, corrections due to atomic physics effects which could affect the splitting and broadening of the spectral Dα line and lead to misinterpretation of the spectra are evaluated. The first measurements of the edge main ion diagnostic are also presented.Spanish Ministry of Science, Innovation and Universities (grant FPU17/06273)H2020 Marie-Sklodowska Curie programme (Grant No. 708257)Spanish Ministry of Economy and Competitiveness (Grant No. FJCI-201422139)EUROfusion Consortium grant agreement No 63305