Attention deficit/hyperactivity disorder (ADHD) is a risk factor for tobacco use and dependence. This study examines the responsiveness to nicotine of an adolescent model of ADHD, the spontaneously hypertensive rat (SHR). The conditioned place preference (CPP) procedure was used to assess nicotine-induced locomotion and conditioned reward in SHR and the Wistar Kyoto (WKY) control strain over a range of nicotine doses (0.0, 0.1, 0.3 and 0.6 mg/kg). Prior to conditioning, SHRs were more active and less biased toward one side of the CPP chamber than WKY rats. Following conditioning, SHRs developed CPP to the highest dose of nicotine (0.6 mg/kg), whereas WKYs did not develop CPP to any nicotine dose tested. During conditioning, SHRs displayed greater locomotor activity in the nicotine-paired compartment than in the saline-paired compartment across conditioning trials. SHRs that received nicotine (0.1, 0.3, 0.6 mg/kg) in the nicotine-paired compartment showed an increase in locomotor activity between conditioning trials. Nicotine did not significantly affect WKY locomotor activity. These findings suggest that the SHR strain is a suitable model for studying ADHD-related nicotine use and dependence, but highlights potential limitations of the WKY control strain and the CPP procedure for modeling ADHD-related nicotine reward.

Atmospheric radiocarbon (¹⁴C) represents an important observational constraint on emissions of fossil-fuel derived carbon into the atmosphere due to the absence of ¹⁴C in fossil fuel reservoirs. The high sensitivity and precision that accelerator mass spectrometry (AMS) affords in atmospheric ¹⁴C analysis has greatly increased the potential for using such measurements to evaluate bottom-up emissions inventories of fossil fuel CO₂(CO₂ff), as well as those for other co-emitted species. Here we use observations of ¹⁴CO₂ and a series of primary hydrocarbons and combustion tracers from discrete air samples collected between June 2009 and September 2010 at the National Oceanic and Atmospheric Administration Boulder Atmospheric Observatory (BAO; Lat: 40.050° N, Lon: 105.004° W) to derive emission ratios of each species with respect to CO₂ff. The BAO tower is situated at the boundary of the Denver metropolitan area to the south and a large industrial and agricultural region to the north and east, making it an ideal location to study the contrasting mix of emissions from the activities in each region. The species considered in this analysis are carbon monoxide (CO), methane (CH₄), acetylene (C₂H₂), benzene (C₆H₆), and C₃–C₅ alkanes. We estimate emissions for a subset of these species by using the Vulcan high resolution CO2ff emission data product as a reference. We find that CO is overestimated in the 2008 National Emissions Inventory (NEI08) by a factor of ~2. A close evaluation of the inventory suggests that the ratio of CO emitted per unit fuel burned from on-road gasoline vehicles is likely over-estimated by a factor of 2.5. Using a wind-directional analysis of the data, we find enhanced concentrations of CH₄, relative to CO₂ff, in air influenced by emissions to the north and east of the BAO tower when compared to air influenced by emissions in the Denver metro region to the south. Along with enhanced CH₄, the strongest enhancements of the C₃–C₅ alkanes are also found in the north and east wind sector, suggesting that both the alkane and CH₄ enhancements are sourced from oil and gas fields located to the northeast, though it was not possible to rule out the contribution of non oil and gas CH₄ sources.

Urban environments are the primary contributors to global anthropogenic carbon emissions. Because much of the growth in CO₂ emissions will originate from cities, there is a need to develop, assess, and improve measurement and modeling strategies for quantifying and monitoring greenhouse gas emissions from large urban centers. In this study the uncertainties in an aircraft-based mass balance approach for quantifying carbon dioxide and methane emissions from an urban environment, focusing on Indianapolis, IN, USA, are described. The relatively level terrain of Indianapolis facilitated the application of mean wind fields in the mass balance approach. We investigate the uncertainties in our aircraft-based mass balance approach by (1) assessing the sensitivity of the measured flux to important measurement and analysis parameters including wind speed, background CO₂ and CH₄, boundary layer depth, and interpolation technique, and (2) determining the flux at two or more downwind distances from a point or area source (with relatively large source strengths such as solid waste facilities and a power generating station) in rapid succession, assuming that the emission flux is constant. When we quantify the precision in the approach by comparing the estimated emissions derived from measurements at two or more downwind distances from an area or point source, we find that the minimum and maximum repeatability were 12 and 52%, with an average of 31%. We suggest that improvements in the experimental design can be achieved by careful determination of the background concentration, monitoring the evolution of the boundary layer through the measurement period, and increasing the number of downwind horizontal transect measurements at multiple altitudes within the boundary layer.

Large urban emissions of greenhouse gases result in large atmospheric enhancements relative to background that are easily measured. Using CO₂ mole fractions and Δ¹⁴C and δ¹³C values of CO₂ in the Los Angeles megacity observed in inland Pasadena (2006–2013) and coastal Palos Verdes peninsula (autumn 2009–2013), we have determined time series for CO₂ contributions from fossil fuel combustion (C_ff) for both sites and broken those down into contributions from petroleum and/or gasoline and natural gas burning for Pasadena. We find a 10 % reduction in Pasadena C_ff during the Great Recession of 2008–2010, which is consistent with the bottom-up inventory determined by the California Air Resources Board. The isotopic variations and total atmospheric CO₂ from our observations are used to infer seasonality of natural gas and petroleum combustion. The trend of CO₂ contributions to the atmosphere from natural gas combustion is out of phase with the seasonal cycle of total natural gas combustion seasonal patterns in bottom-up inventories but is consistent with the seasonality of natural gas usage by the area's electricity generating power plants. For petroleum, the inferred seasonality of CO₂ contributions from burning petroleum is delayed by several months relative to usage indicated by statewide gasoline taxes. Using the high-resolution Hestia-LA data product to compare C_ff from parts of the basin sampled by winds at different times of year, we find that variations in observed fossil fuel CO₂ reflect seasonal variations in wind direction. The seasonality of the local CO₂ excess from fossil fuel combustion along the coast, on Palos Verdes peninsula, is higher in autumn and winter than spring and summer, almost completely out of phase with that from Pasadena, also because of the annual variations of winds in the region. Variations in fossil fuel CO₂ signals are consistent with sampling the bottom-up Hestia-LA fossil CO₂ emissions product for sub-city source regions in the LA megacity domain when wind directions are considered.

Synthetic cathinones, colloquially referred to as “bath salts,” are derivatives of the psychoactive alkaloid cathinone found in Catha edulis (Khat). Since the mid-to-late 2000s, these amphetamine-like psychostimulants have gained popularity amongst drug users due to their potency, low cost, ease of procurement, and constantly evolving chemical structures. Concomitant with their increased use is the emergence of a growing collection of case reports of bizarre and dangerous behaviors, toxicity to numerous organ systems, and death. However, scientific information regarding the abuse liability of these drugs has been relatively slower to materialize. Recently we have published several studies demonstrating that laboratory rodents will readily self-administer the “first generation” synthetic cathinones methylenedioxypyrovalerone (MDPV) and methylone via the intravenous route, in patterns similar to those of methamphetamine. Under progressive ratio schedules of reinforcement, the rank order of reinforcing efficacy of these compounds is MDPV ≥ methamphetamine > methylone. MDPV and methylone, as well as the “second generation” synthetic cathinones α-pyrrolidinovalerophenone (α-PVP) and 4-methylethcathinone (4-MEC), also dose-dependently increase brain reward function. Collectively, these findings indicate that synthetic cathinones have a high abuse and addiction potential and underscore the need for future assessment of the extent and duration of neurotoxicity induced by these emerging drugs of abuse.

Recent advances in fossil fuel CO₂ (FFCO₂) emission inventories enable sensitivity tests of simulated atmospheric CO₂ concentrations to sub-annual variations in FFCO₂ emissions and what this implies for the interpretation of observed CO₂. Six experiments are conducted to investigate the potential impact of three cycles of FFCO₂ emission variability (diurnal, weekly and monthly) using a global tracer transport model. Results show an annual FFCO₂ rectification varying from −1.35 to +0.13 ppm from the combination of all three cycles. This rectification is driven by a large negative diurnal FFCO₂ rectification due to the covariation of diurnal FFCO₂ emissions and diurnal vertical mixing, as well as a smaller positive seasonal FFCO₂ rectification driven by the covariation of monthly FFCO₂ emissions and monthly atmospheric transport. The diurnal FFCO₂ emissions are responsible for a diurnal FFCO₂ concentration amplitude of up to 9.12 ppm at the grid cell scale. Similarly, the monthly FFCO₂ emissions are responsible for a simulated seasonal CO₂ amplitude of up to 6.11 ppm at the grid cell scale. The impact of the diurnal FFCO₂ emissions, when only sampled in the local afternoon, is also important, causing an increase of +1.13 ppmv at the grid cell scale. The simulated CO₂ concentration impacts from the diurnally and seasonally varying FFCO₂ emissions are centered over large source regions in the Northern Hemisphere, extending to downwind regions. This study demonstrates the influence of sub-annual variations in FFCO₂ emissions on simulated CO₂ concentration and suggests that inversion studies must take account of these variations in the affected regions.

The maternal separation (MS) paradigm is an animal model of early life stress. Animals subjected to MS during the first 2 weeks of life display altered behavioral and neuroendocrinological stress responses as adults. MS also produces altered responsiveness to and self-administration (SA) of various drugs of abuse including cocaine, ethanol, and amphetamine. However, no studies have yet examined the effects of MS on methamphetamine (METH) SA. This study was performed to examine the effects of MS on the acquisition of METH SA, extinction, and reinstatement of METH-seeking behavior in adulthood. Given the known influence of early life stress and drug exposure on epigenetic processes, we also investigated group differences in levels of the epigenetic marker methyl CpG binding protein 2 (MeCP2) in the nucleus accumbens (NAc) core. Long–Evans pups and dams were separated on postnatal days (PND) 2–14 for either 180 (MS180) or 15 min (MS15). Male offspring were allowed to acquire METH SA (0.05 mg/kg/infusion) in 15 2-h daily sessions starting at PND67, followed by extinction training and cue-induced reinstatement of METH-seeking behavior. Rats were then assessed for MeCP2 levels in the NAc core by immunohistochemistry. The MS180 group self-administered significantly more METH and acquired SA earlier than the MS15 group. No group differences in extinction or cue-induced reinstatement were observed. MS15 rats had significantly elevated MeCP2-immunoreactive cells in the NAc core as compared to MS180 rats. Together, these data suggest that MS has lasting influences on METH SA as well as epigenetic processes in the brain reward circuitry.

Megacities are major sources of anthropogenic fossil fuel CO₂(FFCO₂) emissions. The spatial extents of these large urban systems cover areas of 10 000 km² or more with complex topography and changing landscapes. We present a high-resolution land–atmosphere modelling system for urban CO₂ emissions over the Los Angeles (LA) megacity area. The Weather Research and Forecasting (WRF)-Chem model was coupled to a very high-resolution FFCO₂ emission product, Hestia-LA, to simulate atmospheric CO₂ concentrations across the LA megacity at spatial resolutions as fine as  ∼  1 km. We evaluated multiple WRF configurations, selecting one that minimized errors in wind speed, wind direction, and boundary layer height as evaluated by its performance against meteorological data collected during the CalNex-LA campaign (May–June 2010). Our results show no significant difference between moderate-resolution (4 km) and high-resolution (1.3 km) simulations when evaluated against surface meteorological data, but the high-resolution configurations better resolved planetary boundary layer heights and vertical gradients in the horizontal mean winds. We coupled our WRF configuration with the Vulcan 2.2 (10 km resolution) and Hestia-LA (1.3 km resolution) fossil fuel CO₂ emission products to evaluate the impact of the spatial resolution of the CO₂ emission products and the meteorological transport model on the representation of spatiotemporal variability in simulated atmospheric CO₂ concentrations. We find that high spatial resolution in the fossil fuel CO₂ emissions is more important than in the atmospheric model to capture CO₂ concentration variability across the LA megacity. Finally, we present a novel approach that employs simultaneous correlations of the simulated atmospheric CO₂ fields to qualitatively evaluate the greenhouse gas measurement network over the LA megacity. Spatial correlations in the atmospheric CO₂ fields reflect the coverage of individual measurement sites when a statistically significant number of sites observe emissions from a specific source or location. We conclude that elevated atmospheric CO₂ concentrations over the LA megacity are composed of multiple fine-scale plumes rather than a single homogenous urban dome. Furthermore, we conclude that FFCO₂ emissions monitoring in the LA megacity requires FFCO₂ emissions modelling with  ∼1 km resolution because coarser-resolution emissions modelling tends to overestimate the observational constraints on the emissions estimates.

We present a high-resolution atmospheric inversion system combining a Lagrangian Particle Dispersion Model (LPDM) and the Weather Research and Forecasting model (WRF), and test the impact of assimilating meteorological observation on transport accuracy. A Four Dimensional Data Assimilation (FDDA) technique continuously assimilates meteorological observations from various observing systems into the transport modeling system, and is coupled to the high resolution CO₂ emission product Hestia to simulate the atmospheric mole fractions of CO₂. For the Indianapolis Flux Experiment (INFLUX) project, we evaluated the impact of assimilating different meteorological observation systems on the linearized adjoint solutions and the CO₂ inverse fluxes estimated using observed CO₂ mole fractions from 11 out of 12 communications towers over Indianapolis for the Sep.-Nov. 2013 period. While assimilating WMO surface measurements improved the simulated wind speed and direction, their impact on the planetary boundary layer (PBL) was limited. Simulated PBL wind statistics improved significantly when assimilating upper-air observations from the commercial airline program Aircraft Communications Addressing and Reporting System (ACARS) and continuous ground-based Doppler lidar wind observations. Wind direction mean absolute error (MAE) decreased from 26 to 14 degrees and the wind speed MAE decreased from 2.0 to 1.2 m s_-1, while the bias remains small in all configurations (< 6 degrees and 0.2 m s_-1). Wind speed MAE and ME are larger in daytime than in nighttime. PBL depth MAE is reduced by ~10%, with little bias reduction. The inverse results indicate that the spatial distribution of CO₂ inverse fluxes were affected by the model performance while the overall flux estimates changed little across WRF simulations when aggregated over the entire domain. Our results show that PBL wind observations are a potent tool for increasing the precision of urban meteorological reanalyses, but that the impact on inverse flux estimates is dependent on the specific urban environment.

Background: 5-HT1B receptor agonists enhance cocaine intake during daily self-administration sessions but decrease cocaine intake when tested after prolonged abstinence. We examined if 5-HT1B receptor agonists produce similar abstinence-dependent effects on methamphetamine intake.

Methods: Male rats were trained to self-administer methamphetamine (0.1 mg/kg, i.v.) on low (fixed ratio 5 and variable ratio 5) and high (progressive ratio) effort schedules of reinforcement until intake was stable. Rats were then tested for the effects of the selective 5-HT1B receptor agonist, CP 94,253 (5.6 or 10 mg/kg), or the less selective but clinically available 5-HT1B/1D receptor agonist, zolmitriptan (10 mg/kg), on methamphetamine self-administration both before and after a 21-day forced abstinence period during which the rats remained in their home cages.

Results: The inverted U-shaped, methamphetamine dose-response function for intake on the fixed ratio 5 schedule was shifted downward by CP 94,253 both before and after abstinence. The CP 94,253-induced decrease in methamphetamine intake was replicated in rats tested on a variable ratio 5 schedule, and the 5-HT1B receptor antagonist SB 224,289 (10 mg/kg) reversed this effect. CP 94,253 also attenuated methamphetamine intake on a progressive ratio schedule both pre- and postabstinence. Similarly, zolmitriptan attenuated methamphetamine intake on a variable ratio 5 schedule both pre- and postabstinence, and the latter effect was sustained after each of 2 more treatments given every 2 to 3 days prior to daily sessions.

Conclusions: Unlike the abstinence-dependent effect of 5-HT1B receptor agonists on cocaine intake reported previously, both CP 94,253 and zolmitriptan decreased methamphetamine intake regardless of abstinence. These findings suggest that 5-HT1B receptor agonists may have clinical efficacy for psychostimulant use disorders.