378 research outputs found

    A psychomotor stimulant theory of addiction.

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    Lateral hypothalamic circuits for feeding and reward

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    In experiments conducted over 60 years ago, the lateral hypothalamic area (LHA) was identified as a critical neuroanatomical substrate for motivated behavior. Electrical stimulation of the LHA induces voracious feeding even in non-restricted animals. In the absence of food, animals will work tirelessly, often lever-pressing 1000’s of times per hour, for electrical stimulation at the same site that provokes feeding, drinking, and other species-typical motivated behaviors. Here we review the classic findings from electrical stimulation studies and integrate them with more recent work that has utilized contemporary circuit-based approaches to study the LHA. We identify specific anatomically and molecularly defined LHA elements that integrate diverse information arising from cortical, extended amygdala, and basal forebrain networks to ultimately generate a highly specified and invigorated behavioral state conveyed via LHA projections to downstream reward and feeding specific circuits

    Failure of Intravenous Morphine to Serve as an Effective Instrumental Reinforcer in Dopamine D2 Receptor Knock-Out Mice

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    The rewarding effects of opiates are thought to be mediated through dopaminergic mechanisms in the ventral tegmental area, dopamine-independent mechanisms in the nucleus accumbens, or both. The purpose of the present study was to explore the contribution of dopamine to opiate-reinforced behavior using D2 receptor knock-out mice. Wild-type, heterozygous, and D2 knock-out mice were first trained to lever press for water reinforcement and then implanted with intravenous catheters. The ability of intravenously delivered morphine to maintain lever pressing in these mice was studied under two schedules of reinforcement: a fixed ratio 4 (FR4) schedule (saline, 0.1, 0.3, or 1.0 mg/kg, per injection) and a progressive ratio (PR) schedule (1.0 mg/kg, per injection). In the wild-type and heterozygous mice, FR4 behavior maintained by morphine injections was significantly greater than behavior maintained by vehicle injections. Response rate was inversely related to injection dose and increased significantly in the wild-type and heterozygous mice when the animals were placed on the PR schedule. In contrast, the knock-out mice did not respond more for morphine than for saline and did not respond more when increased ratios were required by the PR schedule. Thus, morphine served as a positive reinforcer in the wild-type and heterozygous mice but failed to do so in the knock-out mice. Under this range of doses and response requirements, the rewarding effects of morphine appear to depend critically on an intact D2 receptor systemFil: Elmer, Greg I.. University of Maryland; Estados UnidosFil: Pieper, Jeanne O.. National Institutes of Health; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Low, Malcolm J.. Oregon Health and Sciences University; Estados UnidosFil: Grandy, David K.. Oregon Health and Sciences University; Estados UnidosFil: Wise, Roy A.. National Institutes of Health; Estados Unido

    A psychomotor stimulant theory of addiction.

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    Synaptic and Behavioral Profile of Multiple Glutamatergic Inputs to the Nucleus Accumbens

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    Excitatory afferents to the nucleus accumbens (NAc) are thought to facilitate reward seeking by encoding reward-associated cues. Selective activation of different glutamatergic inputs to the NAc can produce divergent physiological and behavioral responses, but mechanistic explanations for these pathway-specific effects are lacking. Here, we compared the innervation patterns and synaptic properties of ventral hippocampus, basolateral amygdala, and prefrontal cortex input to the NAc. Ventral hippocampal input was found to be uniquely localized to the medial NAc shell, where it was predominant and selectively potentiated following cocaine exposure. In vivo, bidirectional optogenetic manipulations of this pathway attenuated and enhanced cocaine-induced locomotion. Challenging the idea that any of these inputs encode motivationally-neutral information, activation of each discrete pathway reinforced instrumental behaviors. Finally, direct optical activation of medium spiny neurons proved to be capable of supporting self-stimulation, demonstrating that behavioral reinforcement is an explicit consequence of strong excitatory drive to the NAc

    Gluon fragmentation to 1D2^1D_2 quarkonia

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    Gluon fragmentation to heavy JPC=2−+J^{PC}=2^{-+} quarkonia is studied herein. We compute these D-wave states' polarized fragmentation functions and find that they are enhanced by large numerical prefactors. The prospects for detecting the lowest lying 1D2^1D_2 charmonium state at the Tevatron are discussed.Comment: 10 pages with 4 uuencoded figures, CALT-68-195

    State-of-the-art in product service-systems

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    A Product Service-System (PSS) is an integrated combination of products and services. This western concept embraces a service-led competitive strategy, environmental sustainability, and the basis to differentiate from competitors who simply offer lower priced products. This paper aims to report the state-of-the-art of PSS research by presenting a clinical review of literature currently available on this topic. The literature is classified and the major outcomes of each study are addressed and analysed. On this basis, this paper defines the PSS concept, reports on its origin and features, gives examples of applications along with potential benefits and barriers to adoption, summarises available tools and methodologies, and identifies future research challenges

    1938: Abilene Christian College Bible Lectures - Full Text

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    Delivered in the Auditorium of Abilene Christian College, February, 1938 Abilene, Texas. Published October, 1939 PRICE, $1.00 FIRM FOUNDATION PUBLISHING HOUSE Austin, Texas

    Gluon fragmentation into polarized charmonium

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    Gluon fragmentation to \chicJ(1P) followed by single photon emission represents the dominant source of prompt J/ΨJ/\Psi's at the Tevatron for p_\perp \gtap 6 \GeV. Since fragmenting gluons are approximately transverse, their products are significantly polarized. We find that gluon fragmentation populates the helicity levels of \chione, \chitwo and J/ΨJ/\Psi according to D_{\chione^{(h=0)}}: D_{\chione^{(|h|=1)}} \simeq 1:1, D_{\chitwo^{(h=0)}} : D_{\chitwo^{(|h|=1)}} : D_{\chitwo^{(|h|=2)}} \simeq 1:2.9:6.0 and D_{\J^{(h=0)}} : D_{\J^{(|h|=1)}} \simeq 1:3.4. We also speculate that gluon fragmentation to the radially excited \chitwo(2P) state followed by subsequent radiative decay could represent a large source of ψ′(2S)\psi'(2S)'s and potentially resolve the ψ′\psi' deficit problem. A measurement of these states' polarizations would test this idea.Comment: 11 pages with 1 uuencoded figure, CALT-68-1943, FERMILAB-PUB-94/256-
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