48 research outputs found

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

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    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

    Incidence of micronuclei in human peripheral blood lymphocytes exposed to modulated and unmodulated 2450 MHz radiofrequency fields

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    Peripheral blood samples from four healthy volunteers were collected and aliquots were exposed in vitro for 2h to either (i) modulated (wideband code division multiple access, WCDMA) or unmodulated continuous wave (CW) 2450MHz radiofrequency (RF) fields at an average specific absorption rate of 10.9W/kg or (ii) sham-exposed. Aliquots of the same samples that were exposed in vitro to an acute dose of 1.5Gy ionizing gamma-radiation (GR) were used as positive controls. Half of the aliquots were treated with melatonin (Mel) to investigate if such treatment offers protection to the cells from the genetic damage, if any, induced by RF and GR. The cells in all samples were cultured for 72h and the lymphocytes were examined to determine the extent of genetic damage assessed from the incidence of micronuclei (MN). The results indicated the following: (i) the incidence of MN was similar in incubator controls, and those exposed to RF/sham and Mel alone; (ii) there were no significant differences between WCDMA and CW RF exposures; (iii) positive control cells exposed to GR alone exhibited significantly increased MN; and (iv) Mel treatment had no effect on cells exposed to RF and sham, while such treatment significantly reduced the frequency of MN in GR-exposed cells
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