Addiction is a Brain Disease

1. Addiction is a Brain Disease Michael L. Johnson, MS Nancy A. Roget, MS

2. Brain Disease • Drug addiction is a brain disease • Every type of psychoactive drug has its own individual mechanism for changing how the brain functions • Drug use changes the individual's brain and its functioning in critical ways Leshner, 2001

3. Addiction is a Brain Disease • Addiction is a Brain Disease BECAUSE: • Using drugs over time changes brain structure and function • Some brain changes may persist after use stops • Long-lasting brain changes effect • cognitive functioning • emotional functioning

4. Addiction is a Brain Disease • Addiction is a brain disease • addicted brain is different from the non-addicted brain • Prolonged drug use causes pervasive changes in brain function

5. Essence of Addiction • Compulsive craving that overwhelms all other motivations (drug use despite negative and social consequences) • root cause of health and social problems

6. Paradox of Addiction Initially Voluntary

7. Addiction’s Similarities with Other Brain Diseases • Some brain diseases are NOT simply biological in nature and expression • Most have social/behavioral aspects • Examples: • Alzheimer's • Schizophrenia • Clinical Depression

8. The Adult Brain, and how it works • An Adult brain weighs about 3 pounds and has billions of cells • Neurons • Glial cells

10. The Brain • Organ on thinking, behavior, homeostasis • Different Areas of the brain regulate different functions • Complex tasks are split up into specialized areas • Damage to these areas leads to specific deficits • “Division of labor” allows for Parallel Processing

11. Brain Region & Function • Splits larger tasks into smaller ones • Component tasks are further broken into sub component tasks • Driving • Seeing • Hearing • Moving

12. Understanding How the Brain Works

13. Understanding How the Brain Works

14. Function of Brain Regions • Brainstem= basic function • Heart rate, breathing, digestion, sleep • Cerebellum =skilled repetitive movements, balance • Limbic System=emotions & motivations • Diencephalon=sensory perception

15. Function of Brain Regions • Cerebral Cortex = thinking, perceiving, producing language • Vision, hearing, touch, movement, smell, thinking & reasoning • Frontal Lobe = social behavior Limbic System • Uses memories, information about how the body is working and sensory input

16. Function and Brain Regions

17. 1848 Railroad worker Explosion- tamping rod Rod entered brain Temperament changes 20 years post accident Correlated accident to behavioral changes Frontal lobe = social behavior Phineas Gage

18. Neurons, Brain Chemistry & Neurotransmission

19. The Neuron • Basic signaling unit of brain • Precise connections allow for different actions • Neurons • Sensory receptors • Muscles

20. Cell Body • Nucleus • Metabolic center • Dendrites • Input from other neurons • Axon • Carry high speed messages away from neuron • Branches into presynaptic terminals The Neuron

21. The Synapse

22. The Synapse

23. N E U R O T R A N S M I T T E R S

24. The S y n a p s e • End of axon • Typical neuron has 1000 synapses with other neurons • Intercellular space between neurons • Synaptic cleft

25. Synapses are Dynamic • Neurons can strengthen synaptic connections • New synapses form (protein synthesis) • Synapses can be lost • Responses to life experiences (and aging) • Cellular basis of learning

26. Synaptic Transmission • Neurons communicate via electrical and chemical signals • Electrical signal converted to a chemical signal– a neurotransmitter • Electrical signal within a neuron is an action potential • Wave-like flow of ions (electrical impulse) down axon • Transient depolarization of axon

27. Synaptic Transmission • At the axon terminal, the electrical impulse leads to release of a neurotransmitter • Stored in vesicles which fuse with the neuronal membrane and release their contents into the cleft

28. Synaptic Transmission • Neurotransmitters diffuse into intercellular space • Bind to receptors on dendrite of another cell • Postsynaptic cell • Receptors are specific Dopamine receptors will only bind dopamine

29. Synaptic Transmission • Chemical binding of transmitter with receptor leads to changes in the post-synaptic cell • May generate an action potential • Post-synaptic cell may use a different neurotransmitter to communicate “down stream”

30. Neurotransmission

31. Synaptic Transmission • After binding, neurotransmitters releases from receptor and goes back into the cleft • Removed by enzymes or reuptake pump/ transporter back into terminal • quick removal of transmitters allow for precise communication between neurons

32. Types of Neurotransmitters • A neuron receives many many messages from connecting neurons • Neuron’s response is the “sum” • Excitatory Transmitters • Lead to (generation of A’s and) stimulate firing of post-synaptic neuron • Inhibitory Transmitters • Lead to decreased firing in post-synaptic neuron

34. Routes of Administration • Inhale • Insuflate • Ingest • Inject • Enema • Contact Absorption (patch)

35. Drug Ingestion

36. ORAL 20 to 30 minutes

37. INHALING 7 to 10 Seconds

38. INJECTING 3 to 5 minutes- skin popping 15 to 30 seconds- IV

39. SNORTING 3 to 5 minutes

40. CONTACT

41. Limbic System Reward System • Nucleus accumbens • Prefrontal cortex • Ventral tegmental area

42. Limbic System • Link between higher cortical activity and the “lower” systems that control emotional behavior • Limbic Lobe • Deep lying structures • amygdala • hippocampus • mamillary bodies

43. Limbic System • Specialized brain areas for producing and regulating PLEASURE • Ventral Tegmental Area • Nucleus Accumbens • Prefrontal Cortex • Areas of Limbic system– amygdala, hippocampus, hypothalamus

44. Limbic System • Generates primitive emotional responses to situations • Allows for SURVIVAL • Identify danger/ threats • Fear and aggression • Identify pleasure– “natural rewards” • Eating • Sex • Social Interaction

45. Reward Path • VTA and NA • Primitive brain stem and limbic areas • Activated by drugs of abuse • Activation of these primitive areas can OVERRIDE more evolved cortical areas

46. Reward Pathway • Also the site of action for addictions • Drugs activate the pathway with force and persistence not seen with natural rewards

47. Drug Effects On Neurotransmission • Alcohol, heroin, nicotine excite the dopamine neurons in the VTA to increase dopamine release

48. Drug Effects on Cell • Increased cAMP levels • Activation of transcription factor CREB and changes in gene expression • Changes in synapses, cell structure and function • The resulting intracellular changes appear to be the molecular and cellular basis of addiction (persistent behavioral abnormalities) Nestler Am J Addiction 2001; 201-217

49. Drug Effects on Cell and Learning • Intracellular changes for addiction the same as for learning • Both activities share intracellular signaling cascades (cAMP) and depend on activity of CREB

50. Drug Effects on Cell and Learning • Learning and addiction show similar changes in neuron morphology • Similar changes at the level of the synapse • Multiple similar changes in the neuron • Long term changes • Addiction is long term Nestler 2001 Science 292 (5525) pp 2266-67