Methylphenidate treatment beyond adolescence maintains increased cocaine self-administration in the spontaneously hypertensive rat model of attention deficit/hyperactivity disorder

Past research with the spontaneously hypertensive rat (SHR) model of attention deficit/hyperactivity disorder showed that adolescent methylphenidate treatment enhanced cocaine abuse risk in SHR during adulthood. The acquisition of cocaine self-administration was faster, and cocaine dose-response functions were shifted upward under fixed-ratio and progressive ratio schedules compared to adult SHR that received adolescent vehicle treatment or to control strains that received adolescent methylphenidate treatment. The current study determined if extending treatment beyond adolescence would ameliorate long-term consequences of adolescent methylphenidate treatment on cocaine abuse risk in adult SHR. Treatments (vehicle or 1.5mg/kg/day oral methylphenidate) began on postnatal day 28. Groups of male SHR were treated with vehicle during adolescence and adulthood, with methylphenidate during adolescence and vehicle during adulthood, or with methylphenidate during adolescence and adulthood. The group receiving adolescent-only methylphenidate was switched to vehicle on P56. Cocaine self-administration began on postnatal day 77, and groups receiving methylphenidate during adolescence and adulthood were treated either 1-h before or 1-h after daily sessions. At baseline under a fixed-ratio 1 schedule, cocaine self-administration (2h sessions; 0.3mg/kg unit dose) did not differ among the four treatment groups. Under a progressive ratio schedule (4.5h maximum session length; 0.01-1.0mg/kg unit doses), breakpoints for self-administered cocaine in SHR receiving the adult methylphenidate treatment 1-h pre-session were not different from the vehicle control group. However, compared to the vehicle control group, breakpoints for self-administered cocaine at the 0.3 and 1.0mg/kg unit doses were greater in adult SHR that received adolescent-only methylphenidate or received methylphenidate that was continued into adulthood and administered 1-h post-session. These findings suggest that extending methylphenidate treatment beyond adolescence does not ameliorate explicitly the long-term consequences of adolescent methylphenidate treatment. Pre-session methylphenidate may mask temporarily the detection of an increase in cocaine self-administration following chronic methylphenidate treatment.R01 DA011716 - NIDA NIH HH

Multiwavelength Monitoring of the Dwarf Seyfert 1 Galaxy NGC 4395. IV. The Variable UV Absorption Lines

We report the detection of variable UV absorption lines in NGC 4395, based on UV observations with the HST STIS carried out in April and July, 2004, as part of a reverberation-mapping campaign. Low-ionization lines of O I, N I, Si II, C II, and Fe II, are present in the low-state spectra (April 2004) at a velocity v_shift=-250 km/s (system A_l), and additional high-ionization lines of C IV and N V appear in the high-state spectra (July 2004) at v_shift=-250 km/s (system A_h) and at v_shift=-840 km/s (system B). The absence of absorption from the low metastable levels of Si II implies a density <~10^3 cm^(-3) for system A_l, indicating a location outside the narrow line region (NLR). System A_h is peculiar as only N V absorption is clearly detected. A high N V/C IV absorption ratio is expected for a high metallicity absorber, but this is excluded here as the metallicity of the host galaxy and of the nuclear gas is significantly subsolar. A simple acceptable model for systems A_h and B is an absorber located between the broad line region (BLR) and the NLR, which absorbs only the continuum and the BLR. At the low-state the strong narrow emission lines of C IV and N V dominate the spectrum, making the absorption invisible. At the high-state the absorbed continuum and BLR emission dominate the spectrum. Thus, the change in the observed absorption does not reflect a change in the absorber, but rather a change in the continuum and BLR emission from behind the absorber, relative to the emission from the NLR in front of the absorber. Studies of the absorption line variability in highly variable objects can thus break the degeneracy in the absorber distance determination inherent to single epoch studies.Comment: Accepted for publication in The Astrophysical Journa

Theory of one-dimensional double-barrier quantum pump in two-frequency signal regime

A one-dimensional system with two $\delta$-like barriers or wells bi-chromaticaly oscillating at frequencies $\omega$ and $2\omega$ is considered. The alternating signal leads to the direct current across the structure (even in a symmetric system). The properties of this quantum pump are studied in a wide range of the system parameters.Comment: 4 pages, 5 figure

Blockade of alpha 2-adrenergic receptors in prelimbic cortex: impact on cocaine self-administration in adult spontaneously hypertensive rats following adolescent atomoxetine treatment

RATIONALE: Research with the spontaneously hypertensive rat (SHR) model of attention deficit/hyperactivity disorder demonstrated that chronic methylphenidate treatment during adolescence increased cocaine self-administration established during adulthood under a progressive ratio (PR) schedule. Compared to vehicle, chronic atomoxetine treatment during adolescence failed to increase cocaine self-administration under a PR schedule in adult SHR. OBJECTIVES: We determined if enhanced noradrenergic transmission at α2-adrenergic receptors within prefrontal cortex contributes to this neutral effect of adolescent atomoxetine treatment in adult SHR. METHODS: Following treatment from postnatal days 28–55 with atomoxetine (0.3 mg/kg) or vehicle, adult male SHR and control rats from Wistar-Kyoto (WKY) and Wistar (WIS) strains were trained to self-administer 0.3 mg/kg cocaine. Self-administration performance was evaluated under a PR schedule of cocaine delivery following infusion of the α2-adrenergic receptor antagonist idazoxan (0 and 10–56 μg/side) directly into prelimbic cortex. RESULTS: Adult SHR attained higher PR break points and had greater numbers of active lever responses and infusions than WKY and WIS. Idazoxan dose-dependently increased PR break points and active lever responses in SHR following adolescent atomoxetine vs. vehicle treatment. Behavioral changes were negligible after idazoxan pretreatment in SHR following adolescent vehicle or in WKY and WIS following adolescent atomoxetine or vehicle. CONCLUSIONS: α2-Adrenergic receptor blockade in prelimbic cortex of SHR masked the expected neutral effect of adolescent atomoxetine on adult cocaine self-administration behavior. Moreover, greater efficacy of acute idazoxan challenge in adult SHR after adolescent atomoxetine relative to vehicle is consistent with the idea that chronic atomoxetine may downregulate presynaptic α2A-adrenergic autoreceptors in SHR.National Institutes of Health grant DA011716. (DA011716 - National Institutes of Health)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5693724/Published versio

Adolescent D-amphetamine treatment in a rodent model of ADHD: pro-cognitive effects during adolescence and cocaine abuse risk during adulthood

Attention-deficit/hyperactivity disorder (ADHD) is comorbid with cocaine abuse. Whereas initiating ADHD medication in childhood does not alter later cocaine abuse risk, initiating medication during adolescence may increase risk. Preclinical work in the Spontaneously Hypertensive Rat (SHR) model of ADHD found that adolescent methylphenidate increased cocaine self-administration in adulthood, suggesting a need to identify alternatively efficacious medications for teens with ADHD. We examined effects of adolescent d-amphetamine treatment on strategy set shifting performance during adolescence and on cocaine self-administration and reinstatement of cocaine-seeking behavior (cue reactivity) during adulthood in male SHR, Wistar- Kyoto (inbred control), and Wistar (outbred control) rats. During the set shift phase, adolescent SHR needed more trials and had a longer latency to reach criterion, made more regressive errors and trial omissions, and exhibited slower and more variable lever press reaction times. d- Amphetamine improved performance only in SHR by increasing choice accuracy and decreasing errors and latency to criterion. In adulthood, SHR self-administered more cocaine, made more cocaine-seeking responses, and took longer to extinguish lever responding than control strains. Adolescent d-amphetamine did not alter cocaine self-administration in adult rats of any strain, but reduced cocaine seeking during the first of seven reinstatement test sessions in adult SHR. These findings highlight utility of SHR in modeling cognitive dysfunction and comorbid cocaine abuse in ADHD. Unlike methylphenidate, d-amphetamine improved several aspects of flexible learning in adolescent SHR and did not increase cocaine intake or cue reactivity in adult SHR. Thus, adolescent d-amphetamine was superior to methylphenidate in this ADHD model

Book Reviews

THE LAW SCHOOL OF TOMORROW: THE PROJECTION OF AN IDEAL. Edited by David Haber and Julius Cohen. SHOULD CHURCHES BE TAXED? By D. B. Robertson. CONSTITUTIONAL LAW FOR POLICE (Police Text Series). By John C Klotter and Jacqueline R. Kanovitz

NEEMO - NASA's Extreme Environment Mission Operations: On to a NEO

During NEEMO missions, a crew of six Aquanauts lives aboard the National Oceanic and Atmospheric Administration (NOAA) Aquarius Underwater Laboratory the world's only undersea laboratory located 5.6 km off shore from Key Largo, Florida. The Aquarius habitat is anchored 62 feet deep on Conch Reef which is a research only zone for coral reef monitoring in the Florida Keys National Marine Sanctuary. The crew lives in saturation for a week to ten days and conducts a variety of undersea EVAs (Extra Vehicular Activities) to test a suite of long-duration spaceflight Engineering, Biomedical, and Geoscience objectives. The crew also tests concepts for future lunar exploration using advanced navigation and communication equipment in support of the Constellation Program planetary exploration analog studies. The Astromaterials Research and Exploration Science (ARES) Directorate and Behavioral Health and Performance (BHP) at NASA/Johnson Space Center (JSC), Houston, Texas support this effort to produce a high-fidelity test-bed for studies of human planetary exploration in extreme environments as well as to develop and test the synergy between human and robotic curation protocols including sample collection, documentation, and sample handling. The geoscience objectives for NEEMO missions reflect the requirements for Lunar Surface Science outlined by the LEAG (Lunar Exploration Analysis Group) and CAPTEM (Curation and Analysis Planning Team for Extraterrestrial Materials) white paper [1]. The BHP objectives are to investigate best meas-ures and tools for assessing decrements in cogni-tive function due to fatigue, test the feasibility study examined how teams perform and interact across two levels, use NEEMO as a testbed for the development, deployment, and evaluation of a scheduling and planning tool. A suite of Space Life Sciences studies are accomplished as well, ranging from behavioral health and performance to immunology, nutrition, and EVA suit design results of which will directly support the investigation of open questions and operational concepts that will enable NASA to continue its plan for planetary exploration

The Total Solar Eclipse of 1869 in Iowa: What Remains Today

On August 7th, 1869, a total solar eclipse was visible in the United States. It carved a path through the heartland, nearly bisecting the state of Iowa as it ran from the northwest corner of the state, through Des Moines, and down through the southeast. As the scientists of the day flocked from universities and observatories on the east coast to the Midwest for a chance to make observations and measurements, many of the teams chose to set up in Iowa. Along the path of the eclipse, the parties built temporary observatories to house their telescopes, or simply picked buildings already standing and pointed the telescopes out the window. When it came time to leave, many of the groups left objects behind. The objects serve as latitude and longitude markers, as well as important historical artifacts. In 2022, many of the artifacts have faded into obscurity, lost to time like so many other relics from the 19th century. The goal of this project is to travel to the cities that the astronomers went to, find their observing sites, and reclaim the artifacts they left for us. Out of the 10 cities I visited in Iowa, and the 18 locations I explored, there were 5 places still standing from 1869

Photocurrent in nanostructures with asymmetric antidots

The steady current induced by electromagnetic field in a 2D system with asymmetric scatterers is studied. The scatterers are assumed to be oriented cuts with one diffusive and another specular sides. Besides, the existence of isotropic impurity scatterers is assumed. This simple model simulates the lattice of half-disk which have been studied numerically recently. The model allows the exact solution in the framework of the kinetic equation. The static current response in the second order of electric field is obtained. The photogalvanic tensor contains both responses to linear and circular polarization of electromagnetic field. The model possesses non-analyticity with regards to the rate of impurity scattering.Comment: 9 pages, 6 figure

Why Large Seeds with Physical Dormancy Become Nondormant Earlier Than Small Ones

Under natural conditions, large seeds with physical dormancy (PY) may become water permeable earlier than small ones. However, the mechanism for this difference has not been elucidated. Thus, our aim was to evaluate the traits associated with PY in seeds of Senna multijuga (Fabaceae) and to propose a mechanism for earlier dormancy-break in large than in small seeds. Two seedlots were collected and each separated into large and small seeds. Seed dry mass, water content, thickness of palisade layer in the hilar and distal regions and the ratio between palisade layer thickness (P) in the lens fissure and seed mass (M) were evaluated. Further, the correlation between seed mass and seed dimensions was investigated. Large seeds had higher dry mass and water content than small seeds. The absolute thickness of the palisade layer in the different regions did not show any trend with seed size; however, large seeds had a lower P:M ratio than small seeds. Seed mass correlated positively with all seed dimensions, providing evidence for a substantially higher volume in large seeds. Since wet, but not dry, high temperatures break PY in sensitive seeds of S. multijuga, the data support our prediction that internal pressure potential in the seed and palisade layer thickness in the water gap (lens), which is related to seed mass (i.e. P:M ratio), act together to modulate the second step (dormancy break) of the two-stage sensitivity cycling model for PY break. In which case, large seeds are predetermined to become water-permeable earlier than small ones