EFFECTS OF VOLUNTARY EXERCISE ON REINSTATEMENT OF COCAINE SEEKING
V Philip
Emory Universitycity: Atlanta country: United States (us)
Grant 5R01DA027535-03 from National Institute On Drug Abuse
Abstract: One of the most challenging aspects of treating drug addiction is preventing relapse due to daily challenges such as stress or exposure to drugs or drug-associated cues. Despite many years of research, no generally accepted pharmacotherapy exists. Aerobic exercise has beneficial effects on both physical and mental health, suggesting that it may also be an effective therapy for the treatment of drug dependence. We and others have shown that activation of the central noradrenergic system is essential for stress-induced and drug-primed reinstatement in the rat model of drug self- administration. We have also discovered that chronic exercise increases expression of the neuropeptide galanin in noradrenergic neurons and impairs stress-induced norepinephrine release. The purpose of this proposal is to test the hypothesis that voluntary exercise can attenuate stress-induced and drug-primed reinstatement of cocaine seeking. In Aim 1 of this proposal, we will determine whether chronic voluntary exercise (wheel running) blunts stress-induced or drug-primed reinstatement of cocaine seeking in rats. In Aim 2, we will determine whether a negative correlation exists between the magnitude of wheel running-induced galanin expression in the noradrenergic locus coeruleus and reinstatement, and whether blockade of galanin signaling reverses the beneficial effects of exercise. In Aim 3, we will further investigate the interaction between exercise-induced galanin expression and norepinephrine release. Drug addiction is a chronic, relapsing disease that is very difficult to treat and places enormous social and economic stress on society. Aerobic exercise is beneficial for many aspects of physical and mental health, and may be beneficial for the treatment of drug dependence. The purpose of this proposal is to assess the effects of aerobic exercise in a rat model of drug relapse, and to investigate potential underlying mechanisms. Completion of these experiments may indicate a new therapy for the treatment of drug addiction
Keywords: Abstinence; acute stress; adrenergic; Adrenergic Agents; Aerobic Exercise; Affect; animal data; Animal Model; Attenuated; Autoreceptors; Brain; Brain region; Cell Nucleus; Chronic; Cocaine; Cocaine Dependences; Cues; Drug abuse; Drug Addiction; Drug Exposure; drug relapse; drug seeking behavior; Economics; effective therapy; Exercise; Exposure to; Extinction (Psychology); Feeling; foot; Galanin; galanin receptor; Gene Expression; Human; human relapse; improved; In Situ Hybridization; in vivo; Individual; Infusion procedures; inhibitor/antagonist; Injection of therapeutic agent; insight; Intravenous infusion procedures; Investigation; Link; locus ceruleus structure; Mediating; Medical; Mental Health; Messenger RNA; Microdialysis; Modeling; Monkeys; neuromechanism; Neurons; Neuropeptides; noradrenergic; Norepinephrine; novel; Pathway interactions; Pharmaceutical Preparations; Pharmacotherapy; Phase; Physical activity; physical conditioning; prevent; Prevention; Process; Prosencephalon; psychologic; public health relevance; Rattus; Recurrent disease; Regimen; Relapse; Research; research study; Resistance; response; Reverse Transcriptase Polymerase Chain Reaction; reward circuitry; Rewards; Rodent Model; Role; Running; sedentary; Self Administration; Shock; Signal Transduction; social; Societies; Stimulus; Stress; substance abuse prevention; System; Testing; Time; Training; transmission process; Treatment outcome; Up-Regulation (Physiology)
Relevance: Drug addiction is a chronic, relapsing disease that is very difficult to treat and places enormous social and economic stress on society. Aerobic exercise is beneficial for many aspects of physical and mental health, and may be beneficial for the treatment of drug dependence. The purpose of this proposal is to assess the effects of aerobic exercise in a rat model of drug relapse, and to investigate potential underlying mechanisms. Completion of these experiments may indicate a new therapy for the treatment of drug addiction
Project start date: 2010-01-15
Project end date: 2014-12-31
Budget start date: 1-JAN-2012
Budget end date: 31-DEC-2012
5R01DA027535-03 (2012): $404842
Sponsored Links Excellgen http://Excellgen.com
EFFECTS OF VOLUNTARY EXERCISE ON REINSTATEMENT OF COCAINE SEEKING
V Philip, Assistant Professor
Emory Universitycity: Atlanta country: United States (us)
Grant 5R01DA027535-02 from National Institute On Drug Abuse
Abstract: One of the most challenging aspects of treating drug addiction is preventing relapse due to daily challenges such as stress or exposure to drugs or drug-associated cues. Despite many years of research, no generally accepted pharmacotherapy exists. Aerobic exercise has beneficial effects on both physical and mental health, suggesting that it may also be an effective therapy for the treatment of drug dependence. We and others have shown that activation of the central noradrenergic system is essential for stress-induced and drug-primed reinstatement in the rat model of drug self- administration. We have also discovered that chronic exercise increases expression of the neuropeptide galanin in noradrenergic neurons and impairs stress-induced norepinephrine release. The purpose of this proposal is to test the hypothesis that voluntary exercise can attenuate stress-induced and drug-primed reinstatement of cocaine seeking. In Aim 1 of this proposal, we will determine whether chronic voluntary exercise (wheel running) blunts stress-induced or drug-primed reinstatement of cocaine seeking in rats. In Aim 2, we will determine whether a negative correlation exists between the magnitude of wheel running-induced galanin expression in the noradrenergic locus coeruleus and reinstatement, and whether blockade of galanin signaling reverses the beneficial effects of exercise. In Aim 3, we will further investigate the interaction between exercise-induced galanin expression and norepinephrine release. Drug addiction is a chronic, relapsing disease that is very difficult to treat and places enormous social and economic stress on society. Aerobic exercise is beneficial for many aspects of physical and mental health, and may be beneficial for the treatment of drug dependence. The purpose of this proposal is to assess the effects of aerobic exercise in a rat model of drug relapse, and to investigate potential underlying mechanisms. Completion of these experiments may indicate a new therapy for the treatment of drug addiction
Keywords: 1, 2-Benzenediol, 4-(2-amino-1-hydroxyethyl)-, (R)-; 8-Azabicyclo(3.2.1)octane-2-carboxylic acid, 3-(benzoyloxy)-8-methyl-, methyl ester, (1R-(exo, exo))-; Abstinence; abuse of drugs; abuses drugs; acute stress; Addiction, Cocaine; Addiction, Drug; adrenergic; Adrenergic Agents; Adrenergic Drugs; Adrenergics; Aerobic Activity; Aerobic Exercise; Affect; animal data; Animal Model; Animal Models and Related Studies; Attenuated; Autoreceptors; behavioral extinction; biological signal transduction; blue nucleus; Brain; Brain region; Cell Communication and Signaling; Cell Nucleus; Cell Signaling; Chemical Dependence; Chronic; Circulatory Collapse; circulatory shock; Cocaine; Cocaine Dependences; Common Rat Strains; Cues; Dependence, Drug; Dependences, Cocaine; Drip Infusions; Drip, Intravenous; Drug abuse; Drug Addiction; Drug Dependency; Drug Exposure; drug relapse; drug seeking behavior; Drug Therapy; drug/agent; Drugs; Economics; effective therapy; Encephalon; Encephalons; Exercise; Exercise, Physical; experiment; experimental research; experimental study; Exposure to; Extinction; Extinction (Psychology); Feeling; feelings; Foot; foot; Fore-Brain; Forebrain; Galanin; Galanin (1-29); galanin receptor; Gene Expression; Genetics, in situ Hybridization; Human; human relapse; Human, General; improved; In Situ Hybridization; in situ Hybridization Staining Method; in vivo; Individual; Infusion; Infusion procedures; Infusions, Intravenous; inhibitor; inhibitor/antagonist; Injection of therapeutic agent; Injections; insight; Intracellular Communication and Signaling; Intravenous infusion procedures; Investigation; IV Infusion; Levarterenol; Levonorepinephrine; Link; locus ceruleus structure; Locus Coeruleus; Mammals, Rats; Man (Taxonomy); Man, Modern; Mediating; Medical; Medication; Mental Health; Mental Hygiene; Messenger RNA; Microdialysis; model organism; Modeling; Monkeys; mRNA; Nerve Cells; Nerve Unit; Nervous System, Brain; Neural Cell; neural mechanism; Neurocyte; neuromechanism; neuronal; Neurons; Neuropeptides; Noradrenaline; noradrenergic; Norepinephrine; novel; Nucleus; Nucleus Pigmentosus Pontis; pathway; Pathway interactions; Pes; Pharmaceutic Preparations; Pharmaceutical Preparations; Pharmacotherapy; Phase; Physical activity; physical conditioning; prevent; preventing; Prevention; Process; Prosencephalon; psychologic; psychological; Psychological Health; public health relevance; Rat; Rattus; Recurrent disease; Regimen; Relapse; Relapsed Disease; Research; research study; Resistance; resistant; response; reverse transcriptase PCR; Reverse Transcriptase Polymerase Chain Reaction; reward circuitry; Rewards; RNA, Messenger; Rodent Model; Role; RT-PCR; RTPCR; Running; sedentary; Self Administration; Shock; Signal Transduction; Signal Transduction Systems; Signaling; social; social role; Societies; Stimulus; Stress; Structure of locus ceruleus; substance abuse prevention; System; System, LOINC Axis 4; Testing; Time; Training; Transmission; transmission process; Treatment outcome; Up-Regulation; Up-Regulation (Physiology); Upregulation
Relevance: Drug addiction is a chronic, relapsing disease that is very difficult to treat and places enormous social and economic stress on society. Aerobic exercise is beneficial for many aspects of physical and mental health, and may be beneficial for the treatment of drug dependence. The purpose of this proposal is to assess the effects of aerobic exercise in a rat model of drug relapse, and to investigate potential underlying mechanisms. Completion of these experiments may indicate a new therapy for the treatment of drug addiction
Project start date: 2010-01-15
Project end date: 2014-12-31
Budget start date: 1-JAN-2011
Budget end date: 31-DEC-2011
PFA/PA: RFA-DA-09-013
5R01DA027535-02 (2011): $384691