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dc.contributorNot Applicableen_US
dc.contributor.authorDUBOCOVICH, MARGARITA L Principal Investigatoren_US
dc.date31-Mar-12en_US
dc.date2011en_US
dc.date.accessioned2011-04-18T21:05:06Zen_US
dc.date.accessioned2011-04-19T18:31:24Z
dc.date.available1-Jul-07en_US
dc.date.available2011-04-18T21:05:06Zen_US
dc.date.available2011-04-19T18:31:24Z
dc.date.issued2011-04-18T21:05:06Zen_US
dc.identifier8048100en_US
dc.identifier5R01DA021870-06en_US
dc.identifier21870en_US
dc.identifier.urihttp://hdl.handle.net/10477/1098
dc.descriptionAcute;Anxiety;Area;Attenuated;Basal Ganglia;base;Behavior;behavioral sensitization;Biological Clocks;Brain;Chronic;circadian behavioral rhythms;circadian pacemaker;Circadian Rhythms;Cocaine;conditioning;Corpus striatum structure;CREB1 gene;Crying;Data;Dependence;depressive symptoms;Development;Dimerization;Dopamine;Dopamine Antagonists;Dopamine D2 Receptor;Dopamine Receptor;dopaminergic neuron;Dose;Endogenous depression;Exposure to;Gene Deletion;Gene Expression;Genes;Genetic;Genetic Transcription;Goals;Haloperidol;Hypothalamic structure;In Vitro;in vivo;Lesion;Ligands;Light;Link;Mammals;Mediating;Medical;Melatonin;Melatonin Receptors;Messenger RNA;Methamphetamine;methamphetamine abuse;Methamphetamine dependence;Moods;Motor Activity;mouse model;Mus;Mutant Strains Mice;Neurons;novel;paralogous gene;Parietal Lobe;Pathway interactions;Periodicity;Peripheral;Pharmaceutical Preparations;Pharmacotherapy;Phase;Phase response curves;Phosphorylation;Play;Prosencephalon;Proteins;psychostimulant;public health medicine (field);Receptor Activation;Receptor, Melatonin, MT1;Receptor, Melatonin, MT2;Research;Research Priority;response;Rewards;Risperidone;Rodent;Role;Running;Signal Transduction;Signaling Molecule;Site;Sleep;Sleep Disorders;Sleeplessness;Slice;suprachiasmatic nucleus;System;Tissues;transcription factor;transmission process;treatment duration;treatment strategy;Withdrawal;en_US
dc.descriptionAmount: $ 276798en_US
dc.description.abstractDESCRIPTION (provided by applicant): The wide spread use of methamphetamine, causing abuse and dependence, is a significant medical, psychiatric, and public health concern. Identifying effective pharmacotherapies for the management of methamphetamine abuse and dependence is a research priority. Methamphetamine use is associated with behavioral sensitization, alterations in sleep and circadian rhythmicity, anxiety, mood changes and irritability either during abuse or upon withdrawal. The goal of this application is to investigate the potential of selective melatonin receptor ligands to attenuate the behavioral sensitization, increase reward behavior and circadian rhythm desynchronization associated with chronic methamphetamine abuse. Melatonin receptors (MTi, MT2) are emerging as targets for the modulation of dopamine-mediated signals, entrainment of disrupted behavioral circadian rhythms and sleep promotion. Neuropharmacological approaches will be used to investigate the role of melatonin receptor (MTi, MT2) activation by endogenous and exogenous melatonin in forebrain areas to modulate methamphetamine-induced locomotor sensitization, reward behavior and dopaminergic signaling through the CREB pathway. The involvement of CLOCK and NPAS-2 genes and melatonin receptors on the mechanism(s) by which chronic methamphetamine induce circadian rhythms disorganization and generates free running activity rhythms will also be investigated. Finally, we will develop mouse models to assess the potency of melatonin and dopamine ligands to entrain methamphetamine-induced suprachiasmatic nucleus independent free running rhythms. Results from these studies should provide the basis for the discovery and development of novel melatonin ligands to alleviate insomnia, circadian sleep disorders and depressive symptoms (endogenous depression) associated with the medical use and abuse of methamphetamine-like drugs.en_US
dc.titleMODULATION OF METHAMPHETAMINE ACTIONS IN THE CNSen_US
dc.typeNIH Grant Awarden_US


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