Attenuated Effects of Opiates in Adolescent vs. Adult Male Rats: Reinforcement, Relapse, and Withdrawal

Adolescence in humans is a vulnerable period for illicit drug use, and teenage onset of drug use is associated with long-term addiction. Adolescent sensitivity to drug reinforcement, relapse, and withdrawal has not been explored thoroughly in animal models, especially considering opiate drugs such as morphine and heroin. The present series of studies profiles adolescent sensitivity to opiates using adolescent and adult male rats to test for age differences in opiate self-administration, reinstatement, withdrawal signs, locomotor sensitization, and even brain activation during drug-seeking. To test for acute sensitivity to the reinforcing effects of morphine or heroin, we compared patterns of self-administration by adolescent vs. adult male rats on various schedules of reinforcement, drug doses, and daily access conditions. Using fixed ratio schedules and short daily access, adolescents self-administered less morphine than adults, an effect commonly interpreted as higher drug sensitivity. In contrast, escalation of morphine intake under long access conditions was similar across ages, as was heroin intake using fixed or progressive ratio schedules of reinforcement. To test for enduring effects of opiates, we compared opiate-seeking in the absence of the drug in tests of extinction responding and cue-induced reinstatement. Regardless of the acute effects of morphine or heroin, all adolescent treatment groups showed attenuated opiate-seeking compared to adults. Next we considered behavioral correlates of reinforcement, drug withdrawal and locomotor sensitization, during and after escalating doses of experimenter-administered heroin. Consistent with attenuated opiate-seeking, adolescents exhibited attenuated somatic and locomotor signs of withdrawal compared with adults, although locomotor sensitization was similar across ages. Finally, the medial prefrontal cortex (mPFC) is a brain region heavily implicated in drug reinforcement, so we used tissue levels of Fos-like immunoreactivity to compare activation of this region by heroin-seeking. Indeed mPFC activation was absent in rats that self-administered heroin as adolescents, but robust in adults. Together these behavioral and neuroanatomical results surprisingly suggest that adolescent male rats are less sensitive than adults to some acute and enduring effects of opiates, and may predict better response profiles among younger human addicts. Through future studies, adolescent rats may provide a new model to help identify treatments for drug abuse

Network Synthesis of Linear Dynamical Quantum Stochastic Systems

The purpose of this paper is to develop a synthesis theory for linear dynamical quantum stochastic systems that are encountered in linear quantum optics and in phenomenological models of linear quantum circuits. In particular, such a theory will enable the systematic realization of coherent/fully quantum linear stochastic controllers for quantum control, amongst other potential applications. We show how general linear dynamical quantum stochastic systems can be constructed by assembling an appropriate interconnection of one degree of freedom open quantum harmonic oscillators and, in the quantum optics setting, discuss how such a network of oscillators can be approximately synthesized or implemented in a systematic way from some linear and non-linear quantum optical elements. An example is also provided to illustrate the theory.Comment: Revised and corrected version, published in SIAM Journal on Control and Optimization, 200

NASA's progress in nuclear electric propulsion technology

The National Aeronautics and Space Administration (NASA) has established a requirement for Nuclear Electric Propulsion (NEP) technology for robotic planetary science mission applications with potential future evolution to systems for piloted Mars vehicles. To advance the readiness of NEP for these challenging missions, a near-term flight demonstration on a meaningful robotic science mission is very desirable. The requirements for both near-term and outer planet science missions are briefly reviewed, and the near-term baseline system established under a recent study jointly conducted by the Lewis Research Center (LeRC) and the Jet Propulsion Laboratory (JPL) is described. Technology issues are identified where work is needed to establish the technology for the baseline system, and technology opportunities which could provide improvement beyond baseline capabilities are discussed. Finally, the plan to develop this promising technology is presented and discussed

8. The 1980s

From the Introduction, “The Changes at ILR that began in the seventies slipped imperceptibly into the eighties, and those that may have originated at that time have, for better or worse, left their mark on the present decade. In other words, dividing history into decades is not a particularly precise way of delineating times. Clearly, there was much gaiety preceding and following the Gay Nineties, as there were certainly many roars heard before and after the Roaring Twenties. Moreover, since the speed of change in academia runs at such a leisurely pace, it is virtually impossible to say exactly when an idea found its way into formal practice. Includes: Introduction; A Dean’s View, 1980-85; Deaning, 1985-88; Robert Risley; and An Advisory Council Perspective

Diversity-Function Relationships Changed in a Long-Term Restoration Experiment

The central tenet of biodiversity-ecosystem function (BEF) theory, that species richness increases function, could motivate restoration practitioners to incorporate a greater number of species into their projects. But it is not yet clear how well BEF theory predicts outcomes of restoration, because it has been developed through tests involving short-run and tightly controlled (e.g., weeded) experiments. Thus, we resampled our 1997 BEF experiment in a restored salt marsh to test for long-term effects of species richness (plantings with 1, 3, and 6 species per 2 x 2 m plot), with multiple ecosystem functions as response variables. Over 11 years, 1- and 6-species assemblages converged on intermediate richness (mean = 3.9 species/ 0.25-m2 plot), and composition changed nonrandomly throughout the site. While three species became rare, the two most productive species became co-dominant. The two dominants controlled and increased shoot biomass, which appeared to decrease species richness. Diversity-function relationships became less positive over 11 years and differed significantly with (a) the species-richness metric (planted vs. measured), and (b) the indicator of function (shoot biomass, height, and canopy layering). The loss of positive relationships between species richness and function in our restored site began soon after we stopped weeding and continued with increasing dominance by productive species. Where species-rich plantings are unlikely to ensure long-term restoration of functions, as in our salt marsh, we recommend dual efforts to establish (1) dominant species that provide high levels of target functions, and (2) subordinate species, which might provide additional functions under current or future conditions

Overcoming barriers to Maori inclusion in the appropriate use of 1080 : final report

Sodium monofluoroacetate (Compound 1080) is used in New Zealand for the control of introduced pests, including possums and rabbits. This is the final report of a research programme aimed at empowering Maori to access research information on the impacts of 1080 on non-target species, ultimately allowing Maori to have a greater role in the appropriate use of 1080. The research reported here was undertaken between August 2005 and May 2006

Sodium fluoroacetate (compound 1080) uptake by Puha, a culturally-important food plant

Sodium fluoroacetate (Compound 1080) is a key tool in the control of possums, and the most extensively used vertebrate pesticide in New Zealand (Livingstone 1994; Morgan 1994a, b; Thomas 1994; Gillies and Pierce 1999; Powlesland et al. 1999; Sherley et al. 1999; Styche and Speed 2002). The most common method of control using this pesticide is via aerial application of cereal or carrot baits containing 1080 (Eason et al. 2000). This is a cost effective means of reducing possum populations by more than 90% (Eason et al. 1994, Veltman and Pinder 2001). Despite the efficiency of aerial 1080 application for reducing possum population numbers, support amongst Māori is mixed. In general, Māori oppose the use of toxins in the environment, despite the benefits to be had through the control of pests. In particular, there is much opposition around the aerial use of 1080 (Ogilvie et al. in press). Para (1999) documented concerns of Māori regarding the fate of 1080 in wild harvested kai (food) species. The risk of secondary poisoning of people using kai resources has previously been identified as key research by the Animal Health Board (AHB), Environmental Risk Management Authority (ERMA) and Māori. During aerial application of 1080 baits, there is the possibility that 1080 may leach from baits and be taken up by nearby plants (Atzert 1971; Rammel and Fleming 1978). More recent laboratory research has shown that 1080 can be taken up by terrestrial and aquatic plants, including Myriophyllum triphyllum, a native aquatic New Zealand plant (Ogilvie et al. 1995); Elodea canadensis, an introduced aquatic species (Ogilvie et al. 1996); and broadleaf and ryegrass, both terrestrial species (Ogilvie et al. 1998). In a field setting where a simulated aerial 1080 operation has been conducted, low concentrations of 1080 were found in Coprosma robusta, or karamuramu, a native species used as medicine by Māori; however no 1080 was found in Asplenium bulbiferum, or pikopiko, a native species commonly consumed by Māori (Ogilvie et al. 2006). This report is part of a research programme conducted to investigate the uptake and persistence of 1080 in watercress and puha. This report focuses only on data generated from the puha component of this work. The watercress component will be reported at a later date.Research was undertaken for the Animal Health Board Inc. (AHB) under Contract R-80694 “Uptake of 1080 by Watercress and Puha” by Lincoln University

Infrared Spectroscopy of a Massive Obscured Star Cluster in the Antennae Galaxies (NGC 4038/4039) with NIRSPEC

We present infrared spectroscopy of the Antennae Galaxies (NGC 4038/4039) with NIRSPEC at the W. M. Keck Observatory. We imaged the star clusters in the vicinity of the southern nucleus (NGC 4039) in 0.39" seeing in K-band using NIRSPEC's slit-viewing camera. The brightest star cluster revealed in the near-IR (M_K(0) = -17.9) is insignificant optically, but coincident with the highest surface brightness peak in the mid-IR (12-18 micron) ISO image presented by Mirabel et al. (1998). We obtained high signal-to-noise 2.03 - 2.45 micron spectra of the nucleus and the obscured star cluster at R ~ 1900. The cluster is very young (4 Myr old), massive (16e6 M_sun), and compact (density ~ 115 M_sun pc^(-3) within a 32 pc half-light radius), assuming a Salpeter IMF (0.1 - 100 M_sun). Its hot stars have a radiation field characterized by T_eff ~ 39,000 K, and they ionize a compact H II region with n_e ~ 1e4 cm^(-3). The stars are deeply embedded in gas and dust (A_V ~ 9-10 mag), and their strong FUV field powers a clumpy photodissociation region with densities n_H >= 1e5 cm^(-3) on scales of up to 200 pc, radiating L[H_2 1-0 S(1)] = 9600 L_sun.Comment: 4 pages, 5 embedded figures. To appear in proceedings of 33d ESLAB Symposium: Star Formation from the Small to the Large Scale, held in Noordwijk, The Netherlands, Nov. 1999. Also available at http://astro.berkeley.edu/~agilber

Positive allosteric modulation as a potential therapeutic strategy in anti-NMDA receptor encephalitis

N-methyl-d-aspartate receptors (NMDARs) are ionotropic glutamate receptors important for synaptic plasticity, memory, and neuropsychiatric health. NMDAR hypofunction contributes to multiple disorders, including anti-NMDAR encephalitis (NMDARE), an autoimmune disease of the CNS associated with GluN1 antibody-mediated NMDAR internalization. Here we characterize the functional/pharmacological consequences of exposure to CSF from female human NMDARE patients on NMDAR function, and we characterize the effects of intervention with recently described positive allosteric modulators (PAMs) of NMDARs. Incubation (48 h) of rat hippocampal neurons of both sexes in confirmed NMDARE patient CSF, but not control CSF, attenuated NMDA-induced current. Residual NMDAR function was characterized by lack of change in channel open probability, indiscriminate loss of synaptic and extrasynaptic NMDARs, and indiscriminate loss of GluN2B-containing and GluN2B-lacking NMDARs. NMDARs tagged with N-terminal pHluorin fluorescence demonstrated loss of surface receptors. Thus, function of residual NMDARs following CSF exposure was indistinguishable from baseline, and deficits appear wholly accounted for by receptor loss. Coapplication of CSF and PAMs of NMDARs (SGE-301 or SGE-550, oxysterol-mimetic) for 24 h restored NMDAR function following 24 h incubation in patient CSF. Curiously, restoration of NMDAR function was observed despite washout of PAMs before electrophysiological recordings. Subsequent experiments suggested that residual allosteric potentiation of NMDAR function explained the persistent rescue. Further studies of the pathogenesis of NMDARE and intervention with PAMs may inform new treatments for NMDARE and other disorders associated with NMDAR hypofunction.SIGNIFICANCE STATEMENTAnti-N-methyl-d-aspartate receptor encephalitis (NMDARE) is increasingly recognized as an important cause of sudden-onset psychosis and other neuropsychiatric symptoms. Current treatment leaves unmet medical need. Here we demonstrate cellular evidence that newly identified positive allosteric modulators of NMDAR function may be a viable therapeutic strategy.</jats:p

The solution structure of a cyclic endothelin antagonist, BQ-123, based on 1H1H and 13H1H three bond oupling constants

AbstractA cyclic pentapeptide endothelin antagonist, cyclo(dTrp-dAsp-Pro-dVal-Leu), recently reported (K. Ishikawa et al., 13th Am. Pept. Symp., Cambridge MA, 1991) has been studied by NMR spectroscopy and molecular modeling. A stable structure has been determined without the use of nuclear Overhauser effects and is based primarily on homonuclear and heteronuclear three bond coupling constants. The 13C-edited TOCSY experiment is demonstrated at natural abundance and ∼30 mM peptide concentrations. Three bond 13C1H coupling constants obtained by this method are shown to reduce the ambiguity in φ angle determination which exists when only interproton coupling constants are used. Three out of four φ angles were determined uniquely by this method and the fourth was reduced to two possible values. The proline φ angle was determined to be −78° based on the 3JHzHα and 3JHzHβ coupling constants. Comparison of amide proton temperature dependence, chemical shifts and vicinal proton coupling constants in a 20% acetonitrile/80% water solvent mixture and in (CD3)2SO indicates that the structure is similar in both solvents