222 research outputs found
Nicotine self-administration and ERK signaling are altered in RasGRF2 knockout mice
Ras/Raf/MEK/ERK (Ras-ERK) signaling has been demonstrated to play a role in the effects of drugs of abuse such as cocaine and alcohol, but has not been extensively examined in nicotine-related reward behaviors. We examined the role of Ras Guanine Nucleotide Releasing Factor 2 (RasGRF2), an upstream mediator of the Ras-ERK signaling pathway, on nicotine self-administration (SA) in RasGRF2 KO and WT mice. We first demonstrated that acute nicotine exposure (0.4 mg/kg) resulted in an increase in phosphorylated ERK1/2 (pERK1/2) in the striatum, consistent with previous reports. We also demonstrated that increases in pERK1/2 resulting from acute (0.4 mg/kg) and repeated (0.4 mg/kg, 10 daily injections) exposure to nicotine in WT mice were not present in RasGRF2 KO mice, confirming that RasGRF2 at least partly regulates the activity of the Ras-ERK signaling pathway following nicotine exposure. We then performed intravenous nicotine SA (0.03 mg/kg/infusion for 10 days) in RasGRF2 KO and WT mice. Consistent with a previous report using cocaine SA, RasGRF2 KO mice demonstrated an increase in nicotine SA relative to WT controls. These findings suggest a role for RasGRF2 in the reinforcing effects of nicotine, and implicate the Ras-ERK signaling pathway as a common mediator of the response to drugs of abuse
The inhibition of RasGRF2, but not RasGRF1, alters cocaine reward in mice
Ras/Raf/MEK/ERK(Ras-ERK) signaling has been implicated in the effects of drugs of abuse. Inhibitors of MEK1/2, the kinases upstream of ERK1/2, have been critical in defining the role of the Ras-ERK cascade in drug-dependent alterations in behavioral plasticity, but the Ras family of small GTPases has not been extensively examined in drug-related behaviors. We examined the role of Ras Guanine Nucleotide Releasing Factor 1(RasGRF1) and 2(RasGRF2), upstream regulators of the Ras-ERK signaling cascade, on cocaine self-administration(SA) in male mice. We first established a role for Ras-ERK signaling in cocaine SA, demonstrating that pERK1/2 is upregulated following SA in C57Bl/6N mice in striatum. We then compared RasGRF1 and RasGRF2 knock-out(KO) mouse lines, demonstrating that cocaine SA in RasGRF2 KO mice was increased relative to wild-type(WT) controls, while RasGRF1 KO and WT mice did not differ. This effect in RasGRF2 mice is likely mediated by the Ras-ERK signaling pathway, as pERK1/2 upregulation following cocaine SA was absent in RasGRF2 KO mice. Interestingly, the lentiviral knockdown of RasGRF2 in the NAc had the opposite effect to that in RasGRF2 KO mice, reducing cocaine SA. We subsequently demonstrated that the MEK inhibitor PD325901 administered peripherally prior to cocaine SA increased cocaine intake, replicating the increase seen in RasGRF2 KO mice, while PD325901 administered into the NAc decreased cocaine intake, similar to the effect seen following lentiviral knockdown of RasGRF2. These data indicate a role for RasGRF2 in cocaine SA in mice that is ERK-dependent, and suggest a differential effect of global versus site-specific RasGRF2 inhibition
Multiplicity Structure of the Hadronic Final State in Diffractive Deep-Inelastic Scattering at HERA
The multiplicity structure of the hadronic system X produced in
deep-inelastic processes at HERA of the type ep -> eXY, where Y is a hadronic
system with mass M_Y< 1.6 GeV and where the squared momentum transfer at the pY
vertex, t, is limited to |t|<1 GeV^2, is studied as a function of the invariant
mass M_X of the system X. Results are presented on multiplicity distributions
and multiplicity moments, rapidity spectra and forward-backward correlations in
the centre-of-mass system of X. The data are compared to results in e+e-
annihilation, fixed-target lepton-nucleon collisions, hadro-produced
diffractive final states and to non-diffractive hadron-hadron collisions. The
comparison suggests a production mechanism of virtual photon dissociation which
involves a mixture of partonic states and a significant gluon content. The data
are well described by a model, based on a QCD-Regge analysis of the diffractive
structure function, which assumes a large hard gluonic component of the
colourless exchange at low Q^2. A model with soft colour interactions is also
successful.Comment: 22 pages, 4 figures, submitted to Eur. Phys. J., error in first
submission - omitted bibliograph
Differential (2+1) Jet Event Rates and Determination of alpha_s in Deep Inelastic Scattering at HERA
Events with a (2+1) jet topology in deep-inelastic scattering at HERA are
studied in the kinematic range 200 < Q^2< 10,000 GeV^2. The rate of (2+1) jet
events has been determined with the modified JADE jet algorithm as a function
of the jet resolution parameter and is compared with the predictions of Monte
Carlo models. In addition, the event rate is corrected for both hadronization
and detector effects and is compared with next-to-leading order QCD
calculations. A value of the strong coupling constant of alpha_s(M_Z^2)=
0.118+- 0.002 (stat.)^(+0.007)_(-0.008) (syst.)^(+0.007)_(-0.006) (theory) is
extracted. The systematic error includes uncertainties in the calorimeter
energy calibration, in the description of the data by current Monte Carlo
models, and in the knowledge of the parton densities. The theoretical error is
dominated by the renormalization scale ambiguity.Comment: 25 pages, 6 figures, 3 tables, submitted to Eur. Phys.
Multi-Jet Event Rates in Deep Inelastic Scattering and Determination of the Strong Coupling Constant
Jet event rates in deep inelastic ep scattering at HERA are investigated
applying the modified JADE jet algorithm. The analysis uses data taken with the
H1 detector in 1994 and 1995. The data are corrected for detector and
hadronization effects and then compared with perturbative QCD predictions using
next-to-leading order calculations. The strong coupling constant alpha_S(M_Z^2)
is determined evaluating the jet event rates. Values of alpha_S(Q^2) are
extracted in four different bins of the negative squared momentum
transfer~\qq in the range from 40 GeV2 to 4000 GeV2. A combined fit of the
renormalization group equation to these several alpha_S(Q^2) values results in
alpha_S(M_Z^2) = 0.117+-0.003(stat)+0.009-0.013(syst)+0.006(jet algorithm).Comment: 17 pages, 4 figures, 3 tables, this version to appear in Eur. Phys.
J.; it replaces first posted hep-ex/9807019 which had incorrect figure 4
Hadron Production in Diffractive Deep-Inelastic Scattering
Characteristics of hadron production in diffractive deep-inelastic
positron-proton scattering are studied using data collected in 1994 by the H1
experiment at HERA. The following distributions are measured in the
centre-of-mass frame of the photon dissociation system: the hadronic energy
flow, the Feynman-x (x_F) variable for charged particles, the squared
transverse momentum of charged particles (p_T^{*2}), and the mean p_T^{*2} as a
function of x_F. These distributions are compared with results in the gamma^* p
centre-of-mass frame from inclusive deep-inelastic scattering in the
fixed-target experiment EMC, and also with the predictions of several Monte
Carlo calculations. The data are consistent with a picture in which the
partonic structure of the diffractive exchange is dominated at low Q^2 by hard
gluons.Comment: 16 pages, 6 figures, submitted to Phys. Lett.
Low Q^2 Jet Production at HERA and Virtual Photon Structure
The transition between photoproduction and deep-inelastic scattering is
investigated in jet production at the HERA ep collider, using data collected by
the H1 experiment. Measurements of the differential inclusive jet
cross-sections dsigep/dEt* and dsigmep/deta*, where Et* and eta* are the
transverse energy and the pseudorapidity of the jets in the virtual
photon-proton centre of mass frame, are presented for 0 < Q2 < 49 GeV2 and 0.3
< y < 0.6. The interpretation of the results in terms of the structure of the
virtual photon is discussed. The data are best described by QCD calculations
which include a partonic structure of the virtual photon that evolves with Q2.Comment: 20 pages, 5 Figure
A Search for Selectrons and Squarks at HERA
Data from electron-proton collisions at a center-of-mass energy of 300 GeV
are used for a search for selectrons and squarks within the framework of the
minimal supersymmetric model. The decays of selectrons and squarks into the
lightest supersymmetric particle lead to final states with an electron and
hadrons accompanied by large missing energy and transverse momentum. No signal
is found and new bounds on the existence of these particles are derived. At 95%
confidence level the excluded region extends to 65 GeV for selectron and squark
masses, and to 40 GeV for the mass of the lightest supersymmetric particle.Comment: 13 pages, latex, 6 Figure
Measurement of Leading Proton and Neutron Production in Deep Inelastic Scattering at HERA
Deep--inelastic scattering events with a leading baryon have been detected by
the H1 experiment at HERA using a forward proton spectrometer and a forward
neutron calorimeter. Semi--inclusive cross sections have been measured in the
kinematic region 2 <= Q^2 <= 50 GeV^2, 6.10^-5 <= x <= 6.10^-3 and baryon p_T
<= MeV, for events with a final state proton with energy 580 <= E' <= 740 GeV,
or a neutron with energy E' >= 160 GeV. The measurements are used to test
production models and factorization hypotheses. A Regge model of leading baryon
production which consists of pion, pomeron and secondary reggeon exchanges
gives an acceptable description of both semi-inclusive cross sections in the
region 0.7 <= E'/E_p <= 0.9, where E_p is the proton beam energy. The leading
neutron data are used to estimate for the first time the structure function of
the pion at small Bjorken--x.Comment: 30 pages, 9 figures, 2 tables, submitted to Eur. Phys.
Measurement of D* Meson Cross Sections at HERA and Determination of the Gluon Density in the Proton using NLO QCD
With the H1 detector at the ep collider HERA, D* meson production cross
sections have been measured in deep inelastic scattering with four-momentum
transfers Q^2>2 GeV2 and in photoproduction at energies around W(gamma p)~ 88
GeV and 194 GeV. Next-to-Leading Order QCD calculations are found to describe
the differential cross sections within theoretical and experimental
uncertainties. Using these calculations, the NLO gluon momentum distribution in
the proton, x_g g(x_g), has been extracted in the momentum fraction range
7.5x10^{-4}< x_g <4x10^{-2} at average scales mu^2 =25 to 50 GeV2. The gluon
momentum fraction x_g has been obtained from the measured kinematics of the
scattered electron and the D* meson in the final state. The results compare
well with the gluon distribution obtained from the analysis of scaling
violations of the proton structure function F_2.Comment: 27 pages, 9 figures, 2 tables, submitted to Nucl. Phys.
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