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

Process evaluation of a web-based intervention aimed at empowerment of disability benefit claimants

<p>Abstract</p> <p>Background</p> <p>The objective of this process evaluation study was to gain insight into the reach, compliance, appreciation, usage barriers, and users' perceived effectiveness of a web-based intervention <url>http://www.wiagesprek.nl</url>. This intervention was aimed at empowerment of disability claimants, prior to the assessment of disability by an insurance physician.</p> <p>Methods</p> <p>Reach was determined by registering claimants exposed to the study's invitation brochures, and by comparing trial participant characteristics with non-participants and nationwide claimant data. Compliance was registered by analyzing weblogs, which were automatically collected during the period of the trial. This made it possible to analyze individual use of the intervention. Appreciation, usage barriers, and users' perceived effectiveness were assessed using an online questionnaire that was sent to participants from the intervention group, 6 weeks after enrolment.</p> <p>Results</p> <p>Only 9% of the target population enrolled in the internet program. Because of selective enrolment, more females, higher educated claimants, and less ethnical minorities were reached. Compliance was ambiguous: out of the 123 participants randomized into the intervention group, a significant proportion (33%) did not use the intervention at all, while, at the same time, many participants (32%) used the intervention for more than two hours (i.e. in approximately two weeks). Overall satisfaction with the intervention was good. Claimants perceived the intervention most effective in increasing knowledge, while also a fair amount of users perceived the intervention effective in gaining right expectations or being able to communicate better with their physician.</p> <p>Conclusions</p> <p>The uptake of the intervention <url>http://www.wiagesprek.nl</url> was disappointing. Specifically, the poor reach and compliance of the intervention resulted in a small proportion of the target population using the intervention as intended. Improvements in the implementation process are desirable to increase the reach and compliance and, thereby possibly, the impact of the intervention.</p> <p>Trial registration</p> <p><a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1414">NTR-1414</a></p

A Contribution to the Study of the Orientation of Etruscan Temples

The aim of the present contribution is to analyse the orientation of Etruscan temples in order to understand whether they followed a certain ratio or whether they were randomlyoriented. After a critical analysis of the data from azimuth measurements, an attempt is made to understand whether this ratio could depend on factors that are of ritualistic character, possibly linked to the sky and precepts of the Etrusca Disciplina which are known to us. In undertaking this study, the author has decided first to give a brief summary of previous studies on the present subject. In the final section of this paper, the author presents the data (collected in a series of field visits during the year 2013) pertaining to the azimuths of Etruscan temples, and furthermore makes some comments on the data analysis and its significance