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

Recent D-T results on TFTR

Routine tritium operation in TFTR has permitted investigations of alpha particle physics in parameter ranges resembling those of a reactor core. ICRF wave physics in a DT plasma and the influence of isotopic mass on supershot confinement have also been studied. Continued progress has been made in optimizing fusion power production in TFTR, using extended machine capability and Li wall conditioning. Performance is currently limited by MHD stability. A new reversed magnetic shear regime is being investigated with reduced core transport and a higher predicted stability limit

Electroweak parameters of the z0 resonance and the standard model

Contains fulltext : 124399.pdf (publisher's version ) (Open Access

Fusion power production from TFTR plasmas fueled with deuterium and tritium.

Peak fusion power production of 6.2±0.4 MW has been achieved in TFTR plasmas heated by deuterium and tritium neutral beams at a total power of 29.5 MW. These plasmas have an inferred central fusion alpha particle density of 1.2×1017 m-3 without the appearance of either disruptive magnetohydrodynamics events or detectable changes in Alfvén wave activity. The measured loss rate of energetic alpha particles agreed with the approximately 5% losses expected from alpha particles which are born on unconfined orbits. © 1994 The American Physical Society

Fusion power production from TFTR plasmas fueled with deuterium and tritium.

Peak fusion power production of 6.2±0.4 MW has been achieved in TFTR plasmas heated by deuterium and tritium neutral beams at a total power of 29.5 MW. These plasmas have an inferred central fusion alpha particle density of 1.2×1017 m-3 without the appearance of either disruptive magnetohydrodynamics events or detectable changes in Alfvén wave activity. The measured loss rate of energetic alpha particles agreed with the approximately 5% losses expected from alpha particles which are born on unconfined orbits. © 1994 The American Physical Society

Confinement and heating of a deuterium-tritium plasma.

The Tomamak Fusion Test reactor has performed initial high-power experiments with the plasma fueled with nominally equal densities of deuterium and tritium. Compared to pure deuterium plasmas, the energy stored in the electron and ions increased by ∼20%. These increases indicate improvements in confinement associated with the use of tritium and possibly heating of electrons by α particles created by the D-T fusion reactions. © 1994 The American Physical Society

Confinement and heating of a deuterium-tritium plasma.

The Tomamak Fusion Test reactor has performed initial high-power experiments with the plasma fueled with nominally equal densities of deuterium and tritium. Compared to pure deuterium plasmas, the energy stored in the electron and ions increased by ∼20%. These increases indicate improvements in confinement associated with the use of tritium and possibly heating of electrons by α particles created by the D-T fusion reactions. © 1994 The American Physical Society

Deuterium and tritium experiments on TFTR

Three campaigns, prior to July 1994, attempted to increase the fusion power in DT plasmas on the Tokamak Fusion Test Reactor (TFTR). The first campaign was dedicated to obtaining >5 MW of fusion power while avoiding MHD events similar to the JET X-event. The second was aimed at producing maximum fusion power irrespective of proximity to MHD limits, and achieved 9 MW limited by a disruption. The third campaign increased the energy confinement time using lithium pellet conditioning while raising the ratio of alpha heating to beam heating

Deuterium and tritium experiments on TFTR

Three campaigns, prior to July 1994, attempted to increase the fusion power in DT plasmas on the Tokamak Fusion Test Reactor (TFTR). The first campaign was dedicated to obtaining >5 MW of fusion power while avoiding MHD events similar to the JET X-event. The second was aimed at producing maximum fusion power irrespective of proximity to MHD limits, and achieved 9 MW limited by a disruption. The third campaign increased the energy confinement time using lithium pellet conditioning while raising the ratio of alpha heating to beam heating

Deuterium and tritium experiments on TFTR

Three campaigns, prior to July 1994, attempted to increase the fusion power in DT plasmas on the Tokamak Fusion Test Reactor (TFTR). The first campaign was dedicated to obtaining >5 MW of fusion power while avoiding MHD events similar to the JET X-event. The second was aimed at producing maximum fusion power irrespective of proximity to MHD limits, and achieved 9 MW limited by a disruption. The third campaign increased the energy confinement time using lithium pellet conditioning while raising the ratio of alpha heating to beam heating