AMPA Receptor Plasticity in Accumbens Core Contributes to Incubation of Methamphetamine Craving

BACKGROUND: The incubation of cue-induced drug craving in rodents provides a model of persistent vulnerability to craving and relapse in human addicts. After prolonged withdrawal, incubated cocaine craving depends on strengthening of nucleus accumbens (NAc) core synapses through incorporation of Ca2+-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (CP-AMPARs). Through metabotropic glutamate receptor 1 (mGluR1)-mediated synaptic depression, mGluR1 positive allosteric modulators remove CP-AMPARs from these synapses and thereby reduce cocaine craving. This study aimed to determine if similar plasticity accompanies incubation of methamphetamine craving. METHODS: Rats self-administered saline or methamphetamine under extended-access conditions. Cue-induced seeking tests demonstrated incubation of methamphetamine craving. After withdrawal periods ranging from 1 to \u3e40 days, rats underwent one of the following procedures: 1) whole-cell patch clamp recordings to characterize AMPAR transmission, 2) intra-NAc core injection of the CP-AMPAR antagonist 1-naphthyl acetyl spermine followed by a seeking test, or 3) systemic administration of a mGluR1 positive allosteric modulator followed by a seeking test. RESULTS: Incubation of methamphetamine craving was associated with CP-AMPAR accumulation in NAc core, and both effects were maximal after ~1 week of withdrawal. Expression of incubated craving was decreased by intra-NAc core 1-naphthyl acetyl spermine injection or systemic mGluR1 positive allosteric modulator administration. CONCLUSIONS: These results are the first to demonstrate a role for the NAc in the incubation of methamphetamine craving and describe adaptations in synaptic transmission associated with this model. They establish that incubation of craving and associated CP-AMPAR plasticity occur much more rapidly during withdrawal from methamphetamine compared with cocaine. However, a common mGluR1-based therapeutic strategy may be helpful for recovering cocaine and methamphetamine addicts

A questionnaire to identify patellofemoral pain in the community: an exploration of measurement properties

Background Community-based studies of patellofemoral pain (PFP) need a questionnaire tool that discriminates between those with and those without the condition. To overcome these issues, we have designed a self-report questionnaire which aims to identify people with PFP in the community. Methods Study designs: comparative study and cross-sectional study. Study population: comparative study: PFP patients, soft-tissue injury patients and adults without knee problems. Cross-sectional study: adults attending a science festival. Intervention: comparative study participants completed the questionnaire at baseline and two weeks later. Cross-sectional study participants completed the questionnaire once. The optimal scoring system and threshold was explored using receiver operating characteristic curves, test-retest reliability using Cohen’s kappa and measurement error using Bland-Altman plots and standard error of measurement. Known-group validity was explored by comparing PFP prevalence between genders and age groups. Results Eighty-four participants were recruited to the comparative study. The receiver operating characteristic curves suggested limiting the questionnaire to the clinical features and knee pain map sections (AUC 0.97 95 % CI 0.94 to 1.00). This combination had high sensitivity and specificity (over 90 %). Measurement error was less than the mean difference between the groups. Test–retest reliability estimates suggest good agreement (N = 51, k = 0.74, 95 % CI 0.52–0.91). The cross-sectional study (N = 110) showed expected differences between genders and age groups but these were not statistically significant. Conclusion A shortened version of the questionnaire, based on clinical features and a knee pain map, has good measurement properties. Further work is needed to validate the questionnaire in community samples

Kepler-16: A Transiting Circumbinary Planet

We report the detection of a planet whose orbit surrounds a pair of low-mass stars. Data from the Kepler spacecraft reveal transits of the planet across both stars, in addition to the mutual eclipses of the stars, giving precise constraints on the absolute dimensions of all three bodies. The planet is comparable to Saturn in mass and size, and is on a nearly circular 229-day orbit around its two parent stars. The eclipsing stars are 20% and 69% as massive as the sun, and have an eccentric 41-day orbit. The motions of all three bodies are confined to within 0.5 degree of a single plane, suggesting that the planet formed within a circumbinary disk.Comment: Science, in press; for supplemental material see http://www.sciencemag.org/content/suppl/2011/09/14/333.6049.1602.DC1/1210923.Doyle.SOM.pd

KELT-1b: A Strongly Irradiated, Highly Inflated, Short Period, 27 Jupiter-mass Companion Transiting a mid-F Star

We present the discovery of KELT-1b, the first transiting low-mass companion from the wide-field Kilodegree Extremely Little Telescope-North (KELT-North) survey. The V=10.7 primary is a mildly evolved, solar-metallicity, mid-F star. The companion is a low-mass brown dwarf or super-massive planet with mass of 27.23+/-0.50 MJ and radius of 1.110+0.037-0.024 RJ, on a very short period (P=1.21750007) circular orbit. KELT-1b receives a large amount of stellar insolation, with an equilibrium temperature assuming zero albedo and perfect redistribution of 2422 K. Upper limits on the secondary eclipse depth indicate that either the companion must have a non-zero albedo, or it must experience some energy redistribution. Comparison with standard evolutionary models for brown dwarfs suggests that the radius of KELT-1b is significantly inflated. Adaptive optics imaging reveals a candidate stellar companion to KELT-1, which is consistent with an M dwarf if bound. The projected spin-orbit alignment angle is consistent with zero stellar obliquity, and the vsini of the primary is consistent with tidal synchronization. Given the extreme parameters of the KELT-1 system, we expect it to provide an important testbed for theories of the emplacement and evolution of short-period companions, and theories of tidal dissipation and irradiated brown dwarf atmospheres.Comment: 30 pages, 19 figures. Submitted to Ap

KELT-2Ab: A Hot Jupiter Transiting the Bright (V=8.77) Primary Star of a Binary System

We report the discovery of KELT-2Ab, a hot Jupiter transiting the bright (V=8.77) primary star of the HD 42176 binary system. The host is a slightly evolved late F-star likely in the very short-lived "blue-hook" stage of evolution, with \teff=6148\pm48{\rm K}, $\log{g}=4.030_{-0.026}^{+0.015}$ and \feh=0.034\pm0.78. The inferred stellar mass is $M_*=1.314_{-0.060}^{+0.063}$\msun\ and the star has a relatively large radius of $R_*=1.836_{-0.046}^{+0.066}$\rsun. The planet is a typical hot Jupiter with period $4.11379\pm0.00001$ days and a mass of $M_P=1.524\pm0.088$\mj\ and radius of $R_P=1.290_{-0.050}^{+0.064}$\rj. This is mildly inflated as compared to models of irradiated giant planets at the $\sim$4 Gyr age of the system. KELT-2A is the third brightest star with a transiting planet identified by ground-based transit surveys, and the ninth brightest star overall with a transiting planet. KELT-2Ab's mass and radius are unique among the subset of planets with $V<9$ host stars, and therefore increases the diversity of bright benchmark systems. We also measure the relative motion of KELT-2A and -2B over a baseline of 38 years, robustly demonstrating for the first time that the stars are bound. This allows us to infer that KELT-2B is an early K-dwarf. We hypothesize that through the eccentric Kozai mechanism KELT-2B may have emplaced KELT-2Ab in its current orbit. This scenario is potentially testable with Rossiter-McLaughlin measurements, which should have an amplitude of $\sim$44 m s$^{-1}$.Comment: 9 pages, 2 tables, 4 figures. A short video describing this paper is available at http://www.youtube.com/watch?v=wVS8lnkXXlE. Revised to reflect the ApJL version. Note that figure 4 is not in the ApJL versio

KELT-3b: A Hot Jupiter Transiting a V=9.8 Late-F Star

We report the discovery of KELT-3b, a moderately inflated transiting hot Jupiter with a mass of 1.477 (-0.067, +0.066) M_J, and radius of 1.345 +/- 0.072 R_J, with an orbital period of 2.7033904 +/- 0.000010 days. The host star, KELT-3, is a V=9.8 late F star with M_* = 1.278 (-0.061, +0.063) M_sun, R_* = 1.472 (-0.067, +0.065) R_sun, T_eff = 6306 (-49, +50) K, log(g) = 4.209 (-0.031, +0.033), and [Fe/H] = 0.044 (-0.082, +0.080), and has a likely proper motion companion. KELT-3b is the third transiting exoplanet discovered by the KELT survey, and is orbiting one of the 20 brightest known transiting planet host stars, making it a promising candidate for detailed characterization studies. Although we infer that KELT-3 is significantly evolved, a preliminary analysis of the stellar and orbital evolution of the system suggests that the planet has likely always received a level of incident flux above the empirically-identified threshold for radius inflation suggested by Demory & Seager (2011).Comment: 12 pages, 12 figures, accepted to Ap

Qatar-2: A K dwarf orbited by a transiting hot Jupiter and a more massive companion in an outer orbit

We report the discovery and initial characterization of Qatar-2b, a hot Jupiter transiting a V = 13.3 mag K dwarf in a circular orbit with a short period, P_ b = 1.34 days. The mass and radius of Qatar-2b are M_p = 2.49 M_j and R_p = 1.14 R_j, respectively. Radial-velocity monitoring of Qatar-2 over a span of 153 days revealed the presence of a second companion in an outer orbit. The Systemic Console yielded plausible orbits for the outer companion, with periods on the order of a year and a companion mass of at least several M_j. Thus Qatar-2 joins the short but growing list of systems with a transiting hot Jupiter and an outer companion with a much longer period. This system architecture is in sharp contrast to that found by Kepler for multi-transiting systems, which are dominated by objects smaller than Neptune, usually with tightly spaced orbits that must be nearly coplanar

KELT-6b: A P~7.9 d Hot Saturn Transiting a Metal-Poor Star with a Long-Period Companion

We report the discovery of KELT-6b, a mildly-inflated Saturn-mass planet transiting a metal-poor host. The initial transit signal was identified in KELT-North survey data, and the planetary nature of the occulter was established using a combination of follow-up photometry, high-resolution imaging, high-resolution spectroscopy, and precise radial velocity measurements. The fiducial model from a global analysis including constraints from isochrones indicates that the V=10.38 host star (BD+31 2447) is a mildly evolved, late-F star with T_eff=6102 \pm 43 K, log(g_*)=4.07_{-0.07}^{+0.04} and [Fe/H]=-0.28 \pm 0.04, with an inferred mass M_*=1.09 \pm 0.04 M_sun and radius R_star=1.58_{-0.09}^{+0.16} R_sun. The planetary companion has mass M_P=0.43 \pm 0.05 M_J, radius R_P=1.19_{-0.08}^{+0.13} R_J, surface gravity log(g_P)=2.86_{-0.08}^{+0.06}, and density rho_P=0.31_{-0.08}^{+0.07} g~cm^{-3}. The planet is on an orbit with semimajor axis a=0.079 \pm 0.001 AU and eccentricity e=0.22_{-0.10}^{+0.12}, which is roughly consistent with circular, and has ephemeris of T_c(BJD_TDB)=2456347.79679 \pm 0.00036 and P=7.845631 \pm 0.000046 d. Equally plausible fits that employ empirical constraints on the host star parameters rather than isochrones yield a larger planet mass and radius by ~4-7%. KELT-6b has surface gravity and incident flux similar to HD209458b, but orbits a host that is more metal poor than HD209458 by ~0.3 dex. Thus, the KELT-6 system offers an opportunity to perform a comparative measurement of two similar planets in similar environments around stars of very different metallicities. The precise radial velocity data also reveal an acceleration indicative of a longer-period third body in the system, although the companion is not detected in Keck adaptive optics images.Comment: Published in AJ, 17 pages, 15 figures, 6 table