Drug Addiction Pharmainfo

2,371 views
2,160 views

Published on

Neuroscince of Drug Addiction by V.Niklesh Rao

Published in: Health & Medicine
1 Comment
4 Likes
Statistics
Notes
No Downloads
Views
Total views
2,371
On SlideShare
0
From Embeds
0
Number of Embeds
7
Actions
Shares
0
Downloads
124
Comments
1
Likes
4
Embeds 0
No embeds

No notes for slide
  • KoobG/NP/dia2/102802jh
  • KoobG/NP/dia6c/041204jh
  • KoobG/MIND/dia1/053006jh
  • Zorrilla ACNP 2001
  • KoobG/NP/dia3/031902jh
  • KoobG/NP/dia2/051605jh
  • KoobG/NP/wor2/062802jh.ppt
  • KoobG/NP/wor2/030104jh
  • KoobG/NP/gra1/100801jh
  • Was: KoobG/NP/dia1/060899jh Became: KoobG/NP/dia2/092502jh
  • KoobG/NP/gra1/010302jh
  • 056KoobG/NP/dia2c/011000jh
  • KoobG/NP/dia2/110304jh
  • 036KoobG/NP/gra10c/030501jh
  • KoobG/MIND/gra1/013106jh
  • WeissB/NP/gra2c/060104jh
  • Zorrilla ACNP 2001
  • KoobGNPdia4c120704jh
  • KoobG/NP/wor2/030104jh
  • Drug Addiction Pharmainfo

    1. 1. The Neuroscience of Drug Addiction and Therapy V.Niklesh Rao Under the guidance of K.Raj Kiran sir Profile link: http://www.pharmainfo.net/nik
    2. 2. <ul><li>Introduction </li></ul><ul><li>Key Definitions </li></ul><ul><li>Reward pathway responsible for Addictive Changes </li></ul><ul><li>Stages of the Addiction Cycle </li></ul><ul><li>Neurochemical Changes Associated with the Drug Use, Dependence and Relapse </li></ul><ul><li>Therapy </li></ul><ul><li>Conclusion </li></ul>Contents
    3. 3. Introduction <ul><li>Alcohol </li></ul><ul><ul><li>18 million Americans abuse or are dependent on Alcohol. </li></ul></ul><ul><li>Smoking </li></ul><ul><li>-- In US, approximately 440,000 persons die per year of a cigarette smoking & attributable illness </li></ul><ul><li>Opioid Dependency </li></ul><ul><ul><li>Dependency has been growing rapidly: </li></ul></ul><ul><ul><ul><li>From 1990 to 2001, the number of people who used prescription painkillers recreationally for the first time grew by 335% to include almost 2.5 million people. </li></ul></ul></ul>Estimated Prevalence Among 15-54 Year Olds of Nonmedical Use and Dependence Among Users (1990-1992) (NCS) Ever Used Prevalence of Dependence Dependence Among Users Tobacco Alcohol Illicit Drugs Cannabis Cocaine Drugs 75.6 91.5 51.0 46.3 16.2 24.1 14.1 7.5 4.2 2.7 31.9 15.4 14.7 9.1 16.7
    4. 4. Key Definitions <ul><li>Drug Addiction — Chronically relapsing disorder that is characterized by a compulsion to seek and take drug, loss of control in limiting intake, and emergence of a negative emotional state (e.g. dysphoria, anxiety, irritability) when access to the drug is prevented (here, defined as the “dark side” of addiction) </li></ul><ul><li>Nucleus Accumbens and Extended Amygdala — Forebrain structures involved in the rewarding effects of drugs of abuse. Composed of central nucleus of the amygdala, bed nucleus of the stria terminalis, and a transition zone in the medial part of the nucleus accumbens </li></ul>Reward pathway responsible for Addictive Changes
    5. 5. Reward pathway responsible for Addictive Changes
    6. 6. Neurochemical Circuitry in Drug Reward
    7. 7. Converging Acute Actions of Drugs of Abuse on the Ventral Tegmental Area and Nucleus Accumbens
    8. 8. Summary- Neurocircuitry of Addiction <ul><li>Reward Circuit - nucleus accumbens and extended amygdala (bed nucleus of the stria terminalis and central nucleus of the amygdala) </li></ul><ul><li>“ Craving” Circuit - dorsal prefrontal cortex, basolateral amygdala </li></ul><ul><li>“ Compulsivity” Circuit - ventral striatum, ventral pallidum,medial thalamic- orbitofrontal cortical loop </li></ul>
    9. 9. Stages of the Addiction Cycle
    10. 10. Stages of the Addiction Cycle
    11. 11. Neurobiological Substrates for the Acute Reinforcing Effects of Drugs of Abuse Neurotransmitter Dopamine Opioid Peptides GABA Glutamate Site Ventral tegmental area, nucleus accumbens Nucleus accumbens, amygdala, ventral tegmental area Amygdala, bed nucleus of stria terminalis Nucleus accumbens Neurochemical Changes Associated with the Drug Use, Dependence and Relapse
    12. 12. Neurotransmitters Implicated in the Motivational Effects of Withdrawal from Drug of Abuse Dopamine … “dysphoria” Serotonin … “dysphoria” GABA … anxiety, panic attacks NPY … anti-stress Dynorphin … “dysphoria” CRF … stress Norepinephrine … stress Glutamate….hyperexcitability Common Molecular Changes Associated with Dependence <ul><li>Dopamine D-2 receptor binding - decreased in human imaging studies in dependent subjects </li></ul><ul><li>CREB ( cyclic adenosine monophosphate response element binding protein) transcription factor - decreased in nucleus accumbens and extended amygdala during the development of dependence </li></ul>Reward Transmitters Implicated in the Positive Motivational Effects of Drugs of Abuse Dopamine Opioid peptides GABA Glutamate Positive Hedonic Effects
    13. 14. Chronic Use: Hedonic Homeostatic Dysregulation Hedonic Scale Normal Affective Response to Drugs/Alcohol Altered Dysregulated Set-Point following chronic drug use Hedonic Set Point is Altered with Chronic Drug Use Initially use to get high… Now use to “ get normal” “ Cravings ” “ Feel good” “ Feel bad”
    14. 15. Animal Models for the Different Stages of the Addiction Cycle <ul><li>Animal Models for the Binge/Intoxication Stage </li></ul><ul><li>1. Oral or intravenous drug self-administration </li></ul><ul><li>2. Brain stimulation reward </li></ul><ul><li>3. Place preference </li></ul><ul><li>Animal models for the Withdrawal/Negative Affect Stage </li></ul><ul><li>1. Brain stimulation reward </li></ul><ul><li>2. Place aversion </li></ul><ul><li>Animal Models for the Transition to Addiction </li></ul><ul><li>1. Dependence-induced drug taking </li></ul><ul><li>2. Escalation in drug self-administration with prolonged access </li></ul><ul><li>3. Drug taking despite aversive consequences </li></ul><ul><li>Animal Models for the Preoccupation/Anticipation (“Craving”) Stage </li></ul><ul><li>1. Drug- induced reinstatement </li></ul><ul><li>2. Cue- induced reinstatement </li></ul><ul><li>3. Alcohol Deprivation Effect </li></ul><ul><li>4. Stress- induced reinstatement </li></ul>
    15. 16. Mood Changes Associated with Plasma Levels of Cocaine during Coca Paste Smoking
    16. 17. Cocaine Self-Administration
    17. 18. Extracellular DA and 5-HT in the Nucleus Accumbens During Cocaine Self-Administration and Withdrawal
    18. 19. CNS Actions of Corticotropin Releasing Factor (CRF)
    19. 20. Ethanol Dependence Induction
    20. 21. Extracellular CRF Levels in the Central Amygdala During Ethanol Withdrawal
    21. 22. Effect of CRF Antagonist D -Phe-CRF 12-41 – Central Nucleus of the Amygdala –
    22. 23. Craving-Type 1 <ul><li>“ Craving”- induced by stimuli that have been paired with ethanol self-administration such as environmental cues </li></ul><ul><li>Termed conditioned positive reinforcement in experimental psychology </li></ul><ul><li>An animal model of craving- type 1 is cue induced reinstatement where a cue previously paired with access to ethanol reinstates responding for a lever that has been extinguished. </li></ul>
    23. 24. Reinstatement Neurobiological Effects of Exposure to Drug-Associated Contextual Stimuli Daily Sessions of Self-Administration SA EXT S - S +
    24. 25. Common Molecular Changes Associated with Dependence <ul><li>Dopamine D-2 receptor binding - decreased in human imaging studies in dependent subjects </li></ul><ul><li>CREB ( cyclic adenosine monophosphate response element binding protein) transcription factor - decreased in nucleus accumbens and extended amygdala during the development of dependence </li></ul><ul><li>Delta-FosB transcription factor -changed during protracted abstinence to drugs of abuse </li></ul>
    25. 26. Key Common Neurocircuitry Elements in Drug Seeking Behavior of Addiction
    26. 27. Craving-Type 1 <ul><li>“ Craving”- induced by stimuli that have been paired with ethanol self-administration such as environmental cues </li></ul><ul><li>Termed conditioned positive reinforcement in experimental psychology </li></ul>Craving-Type 2 <ul><li>State of protracted abstinence in alcoholics weeks after acute withdrawal </li></ul><ul><li>Conceptualized as a state change characterized by anxiety and dysphoria or a residual negative affective state that combines with Craving-Type 1 situations to produce relapse to excessive drinking </li></ul>
    27. 28. Therapy <ul><li>No single treatment is appropriate for all individuals </li></ul><ul><li>Effective treatment attends to multiple needs of the individual, not just his/her drug use </li></ul><ul><li>Treatment must address medical, psychological, social, vocational, and legal problems </li></ul>Duration of Treatment <ul><li>Depends on patient problems/needs </li></ul><ul><li>Less than 90 days is of limited/no effectiveness for residential/outpatient setting </li></ul><ul><li>A minimum of 12 months is required for methadone maintenance </li></ul><ul><li>Longer treatment is often indicated </li></ul>Medical Detoxification <ul><li>Detoxification safely manages the physical symptoms of withdrawa </li></ul><ul><li>lOnly first stage of addiction treatment </li></ul><ul><li>Alone, does little to change long-term drug use </li></ul>
    28. 29. Medications for Alcohol Dependence <ul><li>Disulfiram (Antabuse) </li></ul><ul><li>- FDA approved 1954 </li></ul><ul><li>Naltrexone (ReVia) </li></ul><ul><li>- FDA approved 1994 </li></ul><ul><li>Acamprosate </li></ul><ul><li>- FDA approved 2004 </li></ul>
    29. 30. Therapy Counseling and Other Behavioral Therapies Drug Resistance Skills Replace Drug Using Activities Motivation Problem Solving Skills Interpersonal Relationships
    30. 31. Conclusion <ul><li>Drug abuse is an issue of global concern especially among the youth and adolescent population. </li></ul><ul><li>Drug addiction is the major cause of behavioral disturbances and major cause of criminal activity. </li></ul><ul><li>The main objective of study of neuroscience of drug addiction is to effectively develop therapy for the individuals to rid of their drug seeking behavior and to stabilize their behavior. </li></ul><ul><li>Based on the studies, newer, more effective pharmacotherapeutic strategies may be developed. </li></ul>References <ul><li>www.nida.nih.gov </li></ul><ul><li>www.drugabuse.gov </li></ul><ul><li>National Institute on Alcohol Abuse and Alcoholism </li></ul><ul><li>National Institute on Drug Abuse </li></ul><ul><li>California Society of Addiction Medicine </li></ul><ul><li>RANG & DALE'S PHARMACOLOGY </li></ul><ul><li>Basic and Clinical Pharmacology by Bertram G. Katzung </li></ul><ul><li>Goodman & Gilmann’s Pharmacological Basis of Therapeutics </li></ul>
    31. 32. Acknowledgement <ul><li>I am grateful to our college principal Dr.Y.Srinivasa Rao sir for providing an opportunity to present this seminar and also all the staff members who have extended their help and valuable suggestions and have provided all the help they could, I would especially like to thank my guide K.Raj Kiran sir for thoroughly supporting me to prepare and present my presentation. </li></ul><ul><li>I would like to express my gratitude to pharmainfo.net for giving me an opportunity to present the powerpoint presentation on the chosen topic. </li></ul>Thank You

    ×