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Psychopharmacology: Neurotransmitters, Drugs and Behavior

Psychopharmacology: Neurotransmitters, Drugs and Behavior. A quick review of synaptic action. receptor types (ionotropic and metabotropic) receptor subtypes. Being a neurotransmitter: What does it take?. Exists presynaptically Synthesis enzymes exist presynaptically

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Psychopharmacology: Neurotransmitters, Drugs and Behavior

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  1. Psychopharmacology: Neurotransmitters, Drugs and Behavior

  2. A quick review of synaptic action • receptor types (ionotropic and metabotropic) • receptor subtypes

  3. Being a neurotransmitter: What does it take? • Exists presynaptically • Synthesis enzymes exist presynaptically • Released in response to action potential • Postsynaptic membrane has receptors • Application at synapse produces response • Blockade of release stops synaptic function

  4. The classical neurotransmitters • Amines • Monoamines • catecholamines (dopamine, noradrenaline) • indoleamines (serotonin, melatonin) • Quaternary amines • acetylcholine • amino acids (glutamate, GABA)

  5. Catecholamine synthesis -this is not for torture -understanding synthesis can be important for understanding drug action

  6. Catecholamines Dopamine Subtantia nigra and Parkinson’s disease Mesocorticolimbic system and schizophrenia Receptor specificity

  7. Catecholamines Noradrenergic pathways in the brain -locus coeruleus

  8. Serotonin synthesis

  9. Serotonin Serotonergic pathways in the brain -raphe, 15 subtypes, Prozac and depression

  10. Acetylcholine synthesis

  11. Acetylcholine Cholinergic pathways in the brain -basal forebrain, neuromuscular junction

  12. Amino acids: The workhorses of the neurotransmitter family Glutamate - the primary excitatory neurotransmitter in brains GABA (Gamma-amino-butyric-acid) - the primary inhibitory neurotransmitter

  13. The fabulous glutamate receptor Activation of NMDA receptor can cause changes in the numbers of AMPA receptors – a mechanism for learning?

  14. The fabulous GABA receptor Multiple binding sites

  15. Peptides • Produced in minute quantities • often substances that are also found in areas of body other than brain (vasoactive intestinal polypeptide) • tremendously potent and long-acting (neuromodulatory) • opiates

  16. The opiate story • Opiates have been used for centuries to relieve pain • Pert and Snyder found that opiates bind to receptors in several areas • not until 1975 did we know of endogenous opioids • several varieties of receptors

  17. What is a ‘drug’? • A very vague term • all ingested substances alter bodily function • ‘drug’ is reserved for things that have pronounced effects when ingested in small quantities

  18. Basic classification of drug actions • Agonists stimulate or activate • antagonists prevent

  19. Ways that drugs can agonize • Stimulate release • receptor binding • inhibition of reuptake • inhibition of deactivation • promote synthesis

  20. Ways that drugs can antagonize • Block release • receptor blocker • prevent synthesis

  21. Schizophrenia Affects about 1/100 people Begins in 20’s Often triggered by stress, illness, etc. but there’s also a genetic predisposition

  22. Symptoms of schizophrenia Positive symptoms -hallucinations, delusions, paranoia Negative symptoms -lack of emotion, energy, directedness

  23. The dopamine theory of schizophrenia

  24. Competitive binding

  25. Clinical effectiveness of antipsychotics vs their effectiveness in binding to dopamine receptors

  26. Dopamine receptors in normals and schizophrenics

  27. Beyond dopamine New generation antipsychotics affect serotonin as well Glutamate antagonists can help with negative symptoms Schizophrenia likely affects a host of systems perhaps by disturbing a fundamental balance among neurotransmitters

  28. Alzheimer’s Disease First described by Alois Alzheimer in 1907 Course of disease: -initially, some memory loss (new memories and disorientation -relentlessly progressive until one loses identity

  29. Neuropathology in Alzheimer’s disease

  30. Neurofibrillary tangles Silver stain Paired helical filaments

  31. Formation of NFT’s

  32. Amyloid plaques

  33. Formation of amyloid plaques Amyloid precursor protein

  34. Formation of amyloid plaques

  35. Formation of amyloid plaques

  36. Massive loss of synapses in cortex In addition…. Mild Moderate Severe

  37. Basal forebrain involvement Nucleus basalis of Meynert

  38. Causes Largely unknown -Down’s syndrome link -but strongly inherited forms account for only small proportion -plaques seen in wide variety of disorders acquired by disease (encephalitis, CJD) and accident (punch- drunk syndrome)

  39. Treatments • ‘Cognitive enhancers’ • -Acetylcholinesterase inhibitors to offset loss of cholinergic neurons • NMDA antagonists • -Memantine • -idea here is that part of problem in AD is that chronic release of glutamate prevents NMDA receptors from working properly

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