Corticosterone Regulates Both Naturally Occurring and Cocaine‐Induced Dopamine Signaling by Selectively Decreasing Dopamine Uptake

Stressful and aversive events promote maladaptive reward‐seeking behaviors such as drug addiction by acting, in part, on the mesolimbic dopamine system. Using animal models, data from our laboratory and others show that stress and cocaine can interact to produce a synergistic effect on reward circuitry. This effect is also observed when the stress hormone corticosterone is administered directly into the nucleus accumbens (NAc), indicating that glucocorticoids act locally in dopamine terminal regions to enhance cocaine\u27s effects on dopamine signaling. However, prior studies in behaving animals have not provided mechanistic insight. Using fast‐scan cyclic voltammetry, we examined the effect of systemic corticosterone on spontaneous dopamine release events (transients) in the NAc core and shell in behaving rats. A physiologically relevant systemic injection of corticosterone (2 mg/kg i.p.) induced an increase in dopamine transient amplitude and duration (both voltammetric measures sensitive to decreases in dopamine clearance), but had no effect on the frequency of transient release events. This effect was compounded by cocaine (2.5 mg/kg i.p.). However, a second experiment indicated that the same injection of corticosterone had no detectable effect on the dopaminergic encoding of a palatable natural reward (saccharin). Taken together, these results suggest that corticosterone interferes with naturally occurring dopamine uptake locally, and this effect is a critical determinant of dopamine concentration specifically in situations in which the dopamine transporter is pharmacologically blocked by cocaine

Asteroid fragmentation approaches for modeling atmospheric energy deposition

AbstractDuring asteroid entry, energy is deposited in the atmosphere through thermal ablation and momentum-loss due to aerodynamic drag. Analytic models of asteroid entry and breakup physics are used to compute the energy deposition, which can then be compared against measured light curves and used to estimate ground damage due to airburst events. This work assesses and compares energy deposition results from four existing approaches to asteroid breakup modeling, and presents a new model that combines key elements of those approaches. The existing approaches considered include a liquid drop or “pancake” model where the object is treated as a single deforming body, and a set of discrete fragment models where the object breaks progressively into individual fragments. The new model incorporates both independent fragments and aggregate debris clouds to represent a broader range of fragmentation behaviors and reproduce more detailed light curve features. All five models are used to estimate the energy deposition rate versus altitude for the Chelyabinsk meteor impact, and results are compared with an observationally derived energy deposition curve. Comparisons show that four of the five approaches are able to match the overall observed energy deposition profile, but the features of the combined model are needed to better replicate both the primary and secondary peaks of the Chelyabinsk curve

Gravitational Geons Revisited

A careful analysis of the gravitational geon solution found by Brill and Hartle is made. The gravitational wave expansion they used is shown to be consistent and to result in a gauge invariant wave equation. It also results in a gauge invariant effective stress-energy tensor for the gravitational waves provided that a generalized definition of a gauge transformation is used. To leading order this gauge transformation is the same as the usual one for gravitational waves. It is shown that the geon solution is a self-consistent solution to Einstein's equations and that, to leading order, the equations describing the geometry of the gravitational geon are identical to those derived by Wheeler for the electromagnetic geon. An appendix provides an existence proof for geon solutions to these equations.Comment: 18 pages, ReVTeX. To appear in Physical Review D. Significant changes include more details in the derivations of certain key equations and the addition of an appendix containing a proof of the existence of a geon solution to the equations derived by Wheeler. Also a reference has been added and various minor changes have been mad

Corticosterone Acts in the Nucleus Accumbens to Enhance Dopamine Signaling and Potentiate Reinstatement of Cocaine Seeking

Stressful life events are important contributors to relapse in recovering cocaine addicts, but the mechanisms by which they influence motivational systems are poorly understood. Studies suggest that stress may “set the stage” for relapse by increasing the sensitivity of brain reward circuits to drug-associated stimuli. We examined the effects of stress and corticosterone on behavioral and neurochemical responses of rats to a cocaine prime after cocaine self-administration and extinction. Exposure of rats to acute electric footshock stress did not by itself reinstate drug-seeking behavior but potentiated reinstatement in response to a subthreshold dose of cocaine. This effect of stress was not observed in adrenalectomized animals, and was reproduced in nonstressed animals by administration of corticosterone at a dose that reproduced stress-induced plasma levels. Pretreatment with the glucocorticoid receptor antagonist RU38486 did not block the corticosterone effect. Corticosterone potentiated cocaine-induced increases in extracellular dopamine in the nucleus accumbens (NAc), and pharmacological blockade of NAc dopamine receptors blocked corticosterone-induced potentiation of reinstatement. Intra-accumbens administration of corticosterone reproduced the behavioral effects of stress and systemic corticosterone. Corticosterone treatment acutely decreased NAc dopamine clearance measured by fast-scan cyclic voltammetry, suggesting that inhibition of uptake2-mediated dopamine clearance may underlie corticosterone effects. Consistent with this hypothesis, intra-accumbens administration of the uptake2 inhibitor normetanephrine potentiated cocaine-induced reinstatement. Expression of organic cation transporter 3, a corticosterone-sensitive uptake2 transporter, was detected on NAc neurons. These findings reveal a novel mechanism by which stress hormones can rapidly regulate dopamine signaling and contribute to the impact of stress on drug intake

High accuracy time transfer synchronization

In July 1994, the U.S. Naval Observatory (USNO) Time Service System Engineering Division conducted a field test to establish a baseline accuracy for two-way satellite time transfer synchronization. Three Hewlett-Packard model 5071 high performance cesium frequency standards were transported from the USNO in Washington, DC to Los Angeles, California in the USNO's mobile earth station. Two-Way Satellite Time Transfer links between the mobile earth station and the USNO were conducted each day of the trip, using the Naval Research Laboratory(NRL) designed spread spectrum modem, built by Allen Osborne Associates(AOA). A Motorola six channel GPS receiver was used to track the location and altitude of the mobile earth station and to provide coordinates for calculating Sagnac corrections for the two-way measurements, and relativistic corrections for the cesium clocks. This paper will discuss the trip, the measurement systems used and the results from the data collected. We will show the accuracy of using two-way satellite time transfer for synchronization and the performance of the three HP 5071 cesium clocks in an operational environment

The modules of mental health programs implemented in schools in low- and middle-income countries: findings from a systematic literature review

Background: Secondary schools in low- and middle-income countries (LMICs) provide health promotion, preventive, and early intervention services. Nevertheless, literature indicates that the modules of these services are either adapted or modified from existing mental health programs in developed countries. The literature also highlights the provision of non-comprehensive services (mental health promotion, prevention, and early intervention), in LMICs. These findings inform the need for undertaking this systematic literature review. The aim of this review was thus to identify the modules of school-based mental health programs (SBMHP) that have been implemented in LMICs to guide the development of a culturally sensitive comprehensive mental health program for adolescents in a LMIC country. Methods: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was used to guide this review. The following databases were searched in September 2018, to identify the relevant literature: PubMed, CINAHL, Scopus, Web of Science, PsycINFO, and ERIC. The search was conducted by the first author and reviewed by the authors. Results: Following the screening process, a total of 11 papers were identified and reviewed for quality. The systematic review highlighted that the mental health programs provided in schools included: an introduction module, a communication and relationship module, a psychoeducation module, a cognitive skills module, a behavioral skills module, establishing social networks for recovery and help seeking behavioral activities and a summary/conclusion module. Conclusion: This review sheds light on the characteristics of the programs in LMICs. Two programs were found to be universal in nature. Five programs were directed at key risk factors or at-risk groups, and four were early intervention programs. The review also revealed that only one program out of the 11 programs included modules for parents. The synthesis indicated that all the identified programs were adapted or modified from existing programs. The dearth of comprehensive programs in LMICs was also revealed. Lastly, the review revealed seven modules that can be useful for developing a SBMHP

Estimating risk of emergency room visits for asthma from personal versus fixed site measurements of NO2

Background: We examined the impact of data source and exposure measurement error for ambient NO2 on risk estimates derived from a case-crossover study of emergency room visits for asthma in Windsor, Canada between 2002 and 2009. Methods: Paired personal and fixed-site NO2 data were available from an independent population (47 children and 48 adults) in Windsor between 2005 and 2006. We used linear regression to estimate the relationship and measurement error variance induced between fixed site and personal measurements of NO2, and through a series of simulations, evaluated the potential for a Bayesian model to adjust for this change in scale and measurement error. Finally, we re-analyzed data from the previous case-crossover study adjusting for the estimated change in slope and measurement error. Results: Correlations between paired NO2 measurements were weak (R2≤0.08) and slopes were far from unity (0.0029≤β≤0.30). Adjusting the previous case-crossover analysis suggested a much stronger association between personal NO2 (per 1 ppb) (Odds Ratio (OR)=1.276, 95% Credible Interval (CrI): 1.034, 1.569) and emergency room visits for asthma among children relative to the fixed-site estimate (OR=1.024, 95% CrI 1.004–1.045). Conclusions: Our findings suggest that risk estimates based on fixed-site NO2concentrations may differ substantially from estimates based on personal exposures if the change in scale and/or measurement error is large. In practice, one must always keep the scale being used in mind when interpreting risk estimates and not assume that coefficients for ambient concentrations reflect risks at the personal level