Adolescent D-amphetamine treatment in a rodent model of attention deficit/hyperactivity disorder: impact on cocaine abuse vulnerability in adulthood

RATIONALE: Stimulant medications for attention-deficit/hyperactivity disorder (ADHD) in adolescents remain controversial with respect to later development of cocaine abuse. Past research demonstrated that adolescent methylphenidate treatment increased several aspects of cocaine self-administration during adulthood using the spontaneously hypertensive rat (SHR) model of ADHD. Presently, we determined effects of the alternate stimulant medication, d-amphetamine, on cocaine self-administration. OBJECTIVES: We tested the hypothesis that adolescent d-amphetamine would not increase cocaine self-administration in adult SHR, given that d-amphetamine has a different mechanism of action than methylphenidate. METHODS: A pharmacologically relevant dose of d-amphetamine (0.5 mg/kg) or vehicle was administered throughout adolescence to SHR and two control strains, Wistar-Kyoto (WKY) and Wistar (WIS). Three aspects of cocaine abuse vulnerability were assessed in adulthood after discontinuing adolescent treatments: acquisition rate and dose-related responding under fixed (FR) and progressive (PR) ratio schedules. RESULTS: Adult SHR acquired cocaine self-administration faster and self-administered more cocaine across multiple doses compared to WKY and WIS under FR and PR schedules, indicating that SHR is a reliable animal model of comorbid ADHD and cocaine abuse. Relative to vehicle, SHR and WIS with adolescent d-amphetamine treatment self-administered less cocaine upon reaching acquisition criteria, and WIS additionally acquired cocaine self-administration more slowly and had downward shifts in FR and PR cocaine dose-response curves. WKY with adolescent d-amphetamine treatment acquired cocaine self-administration more quickly relative to vehicle. CONCLUSIONS: In contrast to methylphenidate, adolescent d-amphetamine did not augment cocaine self-administration in SHR. Adolescent d-amphetamine treatment actually protected against cocaine abuse vulnerability in adult SHR and WIS.National Institutes of Health grant DA011716 and the Clara Mayo Memorial Fellowship at Boston University. (DA011716 - National Institutes of Health; Clara Mayo Memorial Fellowship at Boston University)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026317/Published versio

Direct observation of charge inversion by multivalent ions as a universal electrostatic phenomenon

We have directly observed reversal of the polarity of charged surfaces in water upon the addition of tri- and quadrivalent ions using atomic force microscopy. The bulk concentration of multivalent ions at which charge inversion reversibly occurs depends only very weakly on the chemical composition, surface structure, size and lipophilicity of the ions, but is dominated by their valence. These results support the theoretical proposal that spatial correlations between ions are the driving mechanism behind charge inversion.Comment: submitted to PRL, 26-04-2004 Changed the presentation of the theory at the end of the paper. Changed small error in estimate of prefactor ("w" in first version) of equation

Early Huntington's disease affects movements in transformed sensorimotor mappings

This study examined the effect of transformed visual feedback on movement control in Huntington’s disease (HD). Patients in the early stages of HD and controls performed aiming movements towards peripheral targets on a digitizing tablet using an indirect visual control of movement through a monitor and emphasizing precision. In a baseline condition, HD patients were slower but showed few precision problems in aiming. When visual feedback was inverted in both vertical and horizontal axes, patients showed problems in initial and terminal phases of movement where feedback is most critical. When visual feedback was inverted along a single axis as in a mirror-inversion, HD patients showed large deviations and over-corrections before adaptation. Adaptation was similar in both groups. These results suggest that HD impairs on-line error correction in novel movements

Tolerability and safety of the intake of bovine milk oligosaccharides extracted from cheese whey in healthy human adults.

Mechanistic research suggests a unique evolutionary relationship between complex milk oligosaccharides and cognate bifidobacteria enriched in breast-fed infants. Bovine milk oligosaccharides (BMO) were recently identified as structurally and functionally similar to human milk oligosaccharides. The present single-blind three-way crossover study is the first to determine the safety and tolerability of BMO consumption by healthy human participants (n 12) and its effects on faecal microbiota and microbial metabolism. Participants consumed each supplement (placebo-control; low- and high-BMO doses) for eleven consecutive days, followed by a 2-week washout period prior to initiating the next supplement arm. Low and high BMO doses were consumed as 25 and 35 % of each individual's daily fibre intake, respectively. Safety and tolerability were measured using standardised questionnaires on gut and stomach discomfort and stool consistency. Faecal extracts were profiled for bacterial populations by next-generation sequencing (NGS) and bifidobacteria presence was confirmed using quantitative PCR. Urine was analysed for changes in microbial metabolism using nuclear magnetic resonance spectroscopy (1H-NMR). Consumption of both the low and high BMO doses was well tolerated and did not change stool consistency from baseline. Multivariate analysis of the NGS results demonstrated no change in faecal microbiota phyla among the placebo-control and BMO supplement groups. In conclusion, BMO supplementation was well tolerated in healthy adults and has the potential to shift faecal microbiota toward beneficial strains as part of a synbiotic treatment with probiotic cultures that selectively metabolise oligosaccharides

Limitations and challenges of EIT-based monitoring of stroke volume and pulmonary artery pressure.

Electrical impedance tomography (EIT) shows potential for radiation-free and noninvasive hemodynamic monitoring. However, many factors degrade the accuracy and repeatability of these measurements. Our goal is to estimate the impact of this variability on the EIT-based monitoring of two important central hemodynamic parameters: stroke volume (SV) and pulmonary artery pressure (PAP). We performed simulations on a 4D ([Formula: see text]) bioimpedance model of a human volunteer to study the influence of four potential confounding factors (electrode belt displacement, electrode detachment, changes in hematocrit and lung air volume) on the performance of EIT-based SV and PAP estimation. Results were used to estimate how these factors affect the EIT measures of either absolute values or relative changes (i.e. trending). Our findings reveal that the absolute measurement of SV via EIT is very sensitive to electrode belt displacements and lung conductivity changes. Nonetheless, the trending ability of SV EIT might be a promising alternative. The timing-based measurement of PAP is more robust to lung conductivity changes but sensitive to longitudinal belt displacements at severe hypertensive levels and to rotational displacements (independent of the PAP level). We identify and quantify the challenges of EIT-based SV and PAP monitoring. Absolute SV via EIT is challenging, but trending is feasible, while both the absolute and trending of PAP via EIT are mostly impaired by belt displacements

Many-body Theory vs Simulations for the pseudogap in the Hubbard model

The opening of a critical-fluctuation induced pseudogap (or precursor pseudogap) in the one-particle spectral weight of the half-filled two-dimensional Hubbard model is discussed. This pseudogap, appearing in our Monte Carlo simulations, may be obtained from many-body techniques that use Green functions and vertex corrections that are at the same level of approximation. Self-consistent theories of the Eliashberg type (such as the Fluctuation Exchange Approximation) use renormalized Green functions and bare vertices in a context where there is no Migdal theorem. They do not find the pseudogap, in quantitative and qualitative disagreement with simulations, suggesting these methods are inadequate for this problem. Differences between precursor pseudogaps and strong-coupling pseudogaps are also discussed.Comment: Accepted, Phys. Rev. B15 15Mar00. Expanded version of original submission, Latex, 8 pages, epsfig, 5 eps figures (Last one new). Discussion on fluctuation and strong coupling induced pseudogaps expande