Activation instead of blocking mesolimbic dopaminergic reward circuitry is a preferred modality in the long term treatment of reward deficiency syndrome (RDS): a commentary

BACKGROUND AND HYPOTHESIS. Based on neurochemical and genetic evidence, we suggest that both prevention and treatment of multiple addictions, such as dependence to alcohol, nicotine and glucose, should involve a biphasic approach. Thus, acute treatment should consist of preferential blocking of postsynaptic Nucleus Accumbens (NAc) dopamine receptors (D1-D5), whereas long term activation of the mesolimbic dopaminergic system should involve activation and/or release of Dopamine (DA) at the NAc site. Failure to do so will result in abnormal mood, behavior and potential suicide ideation. Individuals possessing a paucity of serotonergic and/or dopaminergic receptors, and an increased rate of synaptic DA catabolism due to high catabolic genotype of the COMT gene, are predisposed to self-medicating any substance or behavior that will activate DA release, including alcohol, opiates, psychostimulants, nicotine, gambling, sex, and even excessive internet gaming. Acute utilization of these substances and/or stimulatory behaviors induces a feeling of well being. Unfortunately, sustained and prolonged abuse leads to a toxic" pseudo feeling" of well being resulting in tolerance and disease or discomfort. Thus, a reduced number of DA receptors, due to carrying the DRD2 A1 allelic genotype, results in excessive craving behavior; whereas a normal or sufficient amount of DA receptors results in low craving behavior. In terms of preventing substance abuse, one goal would be to induce a proliferation of DA D2 receptors in genetically prone individuals. While in vivo experiments using a typical D2 receptor agonist induce down regulation, experiments in vitro have shown that constant stimulation of the DA receptor system via a known D2 agonist results in significant proliferation of D2 receptors in spite of genetic antecedents. In essence, D2 receptor stimulation signals negative feedback mechanisms in the mesolimbic system to induce mRNA expression causing proliferation of D2 receptors. PROPOSAL AND CONCLUSION. The authors propose that D2 receptor stimulation can be accomplished via the use of Synapatmine™, a natural but therapeutic nutraceutical formulation that potentially induces DA release, causing the same induction of D2-directed mRNA and thus proliferation of D2 receptors in the human. This proliferation of D2 receptors in turn will induce the attenuation of craving behavior. In fact as mentioned earlier, this model has been proven in research showing DNA-directed compensatory overexpression (a form of gene therapy) of the DRD2 receptors, resulting in a significant reduction in alcohol craving behavior in alcohol preferring rodents. Utilizing natural dopaminergic repletion therapy to promote long term dopaminergic activation will ultimately lead to a common, safe and effective modality to treat Reward Deficiency Syndrome (RDS) behaviors including Substance Use Disorders (SUD), Attention Deficit Hyperactivity Disorder (ADHD), Obesity and other reward deficient aberrant behaviors. This concept is further supported by the more comprehensive understanding of the role of dopamine in the NAc as a "wanting" messenger in the meso-limbic DA system.LifeGen, Inc.; Electronic Waveform Lab; Huntington Beach and Path Research Foundatio

Studies of the decays D^0 \rightarrow K_S^0K^-\pi^+ and D^0 \rightarrow K_S^0K^+\pi^-

The first measurements of the coherence factor R_{K_S^0K\pi} and the average strong--phase difference \delta^{K_S^0K\pi} in D^0 \to K_S^0 K^\mp\pi^\pm decays are reported. These parameters can be used to improve the determination of the unitary triangle angle \gamma\ in B^- \rightarrow $\widetilde{D}K^-$ decays, where $\widetilde{D}$ is either a D^0 or a D^0-bar meson decaying to the same final state, and also in studies of charm mixing. The measurements of the coherence factor and strong-phase difference are made using quantum-correlated, fully-reconstructed D^0D^0-bar pairs produced in e^+e^- collisions at the \psi(3770) resonance. The measured values are R_{K_S^0K\pi} = 0.70 \pm 0.08 and \delta^{K_S^0K\pi} = (0.1 \pm 15.7)$^\circ$ for an unrestricted kinematic region and R_{K*K} = 0.94 \pm 0.12 and \delta^{K*K} = (-16.6 \pm 18.4)$^\circ$ for a region where the combined K_S^0 \pi^\pm invariant mass is within 100 MeV/c^2 of the K^{*}(892)^\pm mass. These results indicate a significant level of coherence in the decay. In addition, isobar models are presented for the two decays, which show the dominance of the K^*(892)^\pm resonance. The branching ratio {B}(D^0 \rightarrow K_S^0K^+\pi^-)/{B}(D^0 \rightarrow K_S^0K^-\pi^+) is determined to be 0.592 \pm 0.044 (stat.) \pm 0.018 (syst.), which is more precise than previous measurements.Comment: 38 pages. Version 3 updated to include the erratum information. Errors corrected in Eqs (25), (26), 28). Fit results updated accordingly, and external inputs updated to latest best known values. Typo corrected in Eq(3)- no other consequence

Observation of the Dalitz Decay Ds∗+→Ds+e+e−D_{s}^{*+} \to D_{s}^{+} e^{+} e^{-}

Using 586 $\textrm{pb}^{-1}$ of $e^{+}e^{-}$ collision data acquired at $\sqrt{s}=4.170$ GeV with the CLEO-c detector at the Cornell Electron Storage Ring, we report the first observation of $D_{s}^{*+} \to D_{s}^{+} e^{+} e^{-}$ with a significance of $5.3 \sigma$. The ratio of branching fractions \calB(D_{s}^{*+} \to D_{s}^{+} e^{+} e^{-}) / \calB(D_{s}^{*+} \to D_{s}^{+} \gamma) is measured to be $[ 0.72^{+0.15}_{-0.13} (\textrm{stat}) \pm 0.10 (\textrm{syst})]$, which is consistent with theoretical expectations

Updated Measurement of the Strong Phase in D0 --> K+pi- Decay Using Quantum Correlations in e+e- --> D0 D0bar at CLEO

We analyze a sample of 3 million quantum-correlated D0 D0bar pairs from 818 pb^-1 of e+e- collision data collected with the CLEO-c detector at E_cm = 3.77 GeV, to give an updated measurement of \cos\delta and a first determination of \sin\delta, where \delta is the relative strong phase between doubly Cabibbo-suppressed D0 --> K+pi- and Cabibbo-favored D0bar --> K+pi- decay amplitudes. With no inputs from other experiments, we find \cos\delta = 0.81 +0.22+0.07 -0.18-0.05, \sin\delta = -0.01 +- 0.41 +- 0.04, and |\delta| = 10 +28+13 -53-0 degrees. By including external measurements of mixing parameters, we find alternative values of \cos\delta = 1.15 +0.19+0.00 -0.17-0.08, \sin\delta = 0.56 +0.32+0.21 -0.31-0.20, and \delta = (18 +11-17) degrees. Our results can be used to improve the world average uncertainty on the mixing parameter y by approximately 10%.Comment: Minor revisions, version accepted by PR

Higher-order multipole amplitudes in charmonium radiative transitions

Using 24 million $\psi' \equiv \psi(2S)$ decays in CLEO-c, we have searched for higher multipole admixtures in electric-dipole-dominated radiative transitions in charmonia. We find good agreement between our data and theoretical predictions for magnetic quadrupole (M2) amplitudes in the transitions $\psi' \to \gamma \chi_{c1,2}$ and $\chi_{c1,2} \to \gamma J/\psi$, in striking contrast to some previous measurements. Let $b_2^J$ and $a_2^J$ denote the normalized M2 amplitudes in the respective aforementioned decays, where the superscript $J$ refers to the angular momentum of the $\chi_{cJ}$. By performing unbinned maximum likelihood fits to full five-parameter angular distributions, we determine the ratios $a_2^{J=1}/a_2^{J=2} = 0.67^{+0.19}_{-0.13}$ and $a_2^{J=1}/b_2^{J=1} = -2.27^{+0.57}_{-0.99}$, where the theoretical predictions are independent of the charmed quark magnetic moment and are $a_2^{J=1}/a_2^{J=2} = 0.676 \pm 0.071$ and $a_2^{J=1}/b_2^{J=1} = -2.27 \pm 0.16$.Comment: 32 pages, 7 figures, acceptance updat

Search for rare and forbidden decays of charm and charmed-strange mesons to final states h^+- e^-+ e^+

We have searched for flavor-changing neutral current decays and lepton-number-violating decays of D^+ and D^+_s mesons to final states of the form h^+- e^-+ e^+, where h is either \pi or K. We use the complete samples of CLEO-c open-charm data, corresponding to integrated luminosities of 818 pb^-1 at the center-of-mass energy E_CM = 3.774 GeV containing 2.4 x 10^6 D^+D^- pairs and 602 pb^-1 at E_CM = 4.170 GeV containing 0.6 x 10^6 D^*+-_s D^-+_s pairs. No signal is observed in any channel, and we obtain 90% confidence level upper limits on branching fractions B(D^+ --> \pi^+ e^+ e^-) < 5.9 x 10^-6, B(D^+ --> \pi^- e^+ e^+) K^+ e^+ e^-) < 3.0 x 10^-6, B(D^+ --> K^- e^+ e^+) \pi^+ e^+ e^-) < 2.2 x 10^-5, B(D^+_s --> \pi^- e^+ e^+) K^+ e^+ e^-) < 5.2 x 10^-5, and B(D^+_s --> K^- e^+ e^+) < 1.7 x 10^-5.Comment: 9 pages, available through http://www.lns.cornell.edu/public/CLNS

Branching fractions for Y(3S) -> pi^0 h_b and psi(2S) -> pi^0 h_c

Using e^+e^- collision data corresponding to 5.88M Y(3S) [25.9M psi(2S)] decays and acquired by the CLEO III [CLEO-c] detectors operating at CESR, we study the single-pion transitions from Y(3S) [psi(2S)] to the respective spin-singlet states h_{b[c]}. Utilizing only the momentum of suitably selected transition-pi^0 candidates, we obtain the upper limit B(Y(3S) -> pi^0 h_b) < 1.2\times 10^{-3} at 90% confidence level, and measure B(psi(2S) -> pi^0 h_c) = (9.0+-1.5+-1.3)\times 10^{-4}. Signal sensitivities are enhanced by excluding very asymmetric pi^0 -> gamma gamma candidates.Comment: 12 pages 4 figures, version published in Physical Review

Measurement of the eta-Meson Mass using psi(2S) --> eta J/psi

We measure the mass of the eta meson using psi(2S) --> eta J/psi events acquired with the CLEO-c detector operating at the CESR e+e- collider. Using the four decay modes eta --> gamma gamma, 3pi0, pi+pi-pi0, and pi+pi-gamma, we find M(eta)=547.785 +- 0.017 +- 0.057 MeV, in which the first uncertainty is statistical and the second systematic. This result has an uncertainty comparable to the two most precise previous measurements and is consistent with that of NA48, but is inconsistent at the level of 6.5sigma with the much smaller mass obtained by GEM.Comment: 10 pages postscript,also available through http://www.lns.cornell.edu/public/CLNS/2007/, Submitted to PR

Measurement of Interfering K^*+K^- and K^*-K^+ Amplitudes in the Decay D^0 --> K^+K^-pi^0

We have studied the Cabibbo-suppressed decay mode D^0 into K^+ K^- pi^0 using a Dalitz plot technique and find the strong phase difference delta_D [defined as delta_(K*^- K^+) - delta_(K*^+ K^-)] = 332 degrees +- 8 degrees +- 11 degrees and relative amplitude r_D [defined as a_(K*^- K^+) / a_(K*^+ K^-)] = 0.52 +- 0.05 +- 0.04. This measurement indicates significant destructive interference between D^0 into K^+ (K^- pi^0)_K*^- and D^0 into K^- (K^+ pi^0)_K*^+ in the Dalitz plot region where these two modes overlap. This analysis uses 9.0 fb^(-1) of data collected at s^(1/2) of approximately 10.58 GeV with the CLEO III detector.Comment: 10 pages postscript,also available through http://www.lns.cornell.edu/public/CLNS/2006/, Submitted to Phys. Rev. D (Rapid Communications