PHRD5935 Pharm/Tox Lecture 8 - CNS Neurotransmitters

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PHRD5935 Pharm/Tox Lecture 8 - CNS Neurotransmitters
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2014-05-18 20:31:40
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CNS Neurotransmitters
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CNS Neurotransmitters
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  1. brainstem basic fcn
    control of basic functions - respiration, cardiovascular
  2. parts of the brainstem (3)
    • 1) medulla
    • 2) pons
    • 3) midbrain
  3. hypothalamus basic fcn
    regulatory fcns - autonomic control, H2O balance, temperature, eating, circadian rhythm
  4. thalamus basic fcn
    central relay station
  5. amygdala basic fcn
    storage/processing of emotional memories
  6. hippocampus basic fcn
    long-term memory formation

    (esp related to spatial & contextual orientation)
  7. basal ganglia basic fcn
    • initiation of motor activity
    • habitual behavior
  8. cerebellum basic fcn
    control of motor activity
  9. parts of the cerebral cortex (4)
    • 1) parietal lobe
    • 2) occipital lobe
    • 3) temporal lobe
    • 4) frontal lobe
  10. parietal lobe basic fcn
    sensory perception & association
  11. occipital lobe basic fcn
    visual perception
  12. temporal lobe basic fcn (3)
    • visual processing
    • auditory processing
    • long-term memory storage
  13. frontal lobe basic fcn (3)
    • planning, "executive" fcns
    • conscious thought
    • speech, skilled motor control
  14. 3 functions of the blood-brain barrier
    • 1) control of entry substances
    • 2) protects against sudden concentration changes in many substances (eg: ions)
    • 3) protect against infectious agents
  15. 3 main structural features of the BBB
    • 1) tight junctions
    • 2) basal lamina
    • 3) end-feet
  16. BBB endothelial cells that line the blood vessels contact one another with _______ and do not have the pores & fenestrations that peripheral vessels have
    tight junctions
  17. brain capillaries rest on the continuous membrane, the _____ that forms a continuous barrier
    basal lamina
  18. astrocytes send out processes called ____ that surround the outside of the vessels
    end-feet
  19. 3 features entry into the BBB is dictated by
    • 1) transporter molecules
    • 2) endo- & exocytosis
    • 3) hydrophobicity
  20. 3 major dopamine pathways
    • 1) nigrostriatal
    • 2) mesolimbic
    • 3) tuberoinfundibular
  21. nigrostriatal pathway assoc'd structures
    • substantia nigra (origin)
    • striatum (termination)
  22. mesolimbic pathway assoc'd structures
    • ventral tegmental area (origin)
    • prefrontal cortex (termination)
    • nucleus accumbens (termination)
  23. tuberoinfundibular pathway assoc'd structure
    hypothalamus
  24. nigrostriatal pathway involvement in DA pathway
    motor control
  25. tuberoinfundibular pathway involvement in DA pathway
    control of prolactin secretion
  26. mesolimbic pathway involvement in DA pathway
    reward, motivation, pleasure
  27. 5 main sx of Parkinson's disease
    • 1) rhythmical tremor at rest
    • 2) increase in muscle tone
    • 3) difficulty in initiation of movement
    • 4) lack of spontaneous movement (akinesia)
    • 5) slowness of movement (bradykinesia)
  28. underlying pathology of Parkinson's
    loss of the DA neurons leads ultimately to inhibition of outgoing signals from the basal ganglia
  29. how is L-DOPA effective in Parkinson's?
    • L-DOPA is the precursor for the synthesis of DA
    • L-DOPA crosses the BBB, taken up by DA neurons, & converted to DA to increase the amt available for release
  30. 5 main L-DOPA adjuncts
    • 1) carbidopa
    • 2) tolcapone
    • 3) amantadine
    • 4) mirapex
    • 5) selegiline
  31. dopamine decarboxylase (DDC) inhibitor which prevents conversion of L-DOPA to DA in the bloodstream
    carbidopa
  32. blocks catechol-O-methyltransferase (COMT) in the brain which metabolizes L-DOPA
    tolcapone
  33. blocks DA reuptake in the brain to prolong the effects of released DA
    amantadine
  34. selective DA agonists that help boost the effect of released DA
    mirapex
  35. blocks MOA which metabolizes DA
    selegiline
  36. free nerve endings widespread in epidermis & some internal tissues
    nociceptors
  37. what nociceptors respond to
    • mechanical stimulation (stretch)
    • thermal stimulation (heat/cold)
    • chemical stimulation (signaling molecules released due to injury)
  38. 2 types of fibers that make up pain-sensing afferents
    • 1) A
    • 2) C
  39. myelinated, rapid transmission, transmits "sharp" pain (mechanical, thermal) fibers
    A
  40. unmyelinated, slow transmission, transmits "dull" aching pain (mech, thermal, chem)
    C-fibers
  41. 2 types of NT's released from pain-sensing afferents
    • 1) substance P
    • 2) glutamate
  42. - small peptide included in the tachykinin family
    - slow to be removed
    - responsible for progressive intensity & persistence, even after painful stimulus is removed
    substance P
  43. small, "classic" NT released from pain sensing afferents which is removed quickly from the synaptic cleft
    glutamate
  44. 5 main brain structures involved in pain sensation & modulation
    • 1) RVM (rostroventral medulla)
    • 2) periaqueductal gray (PAG)
    • 3) thalamus
    • 4) cortex
    • 5) amygdala
  45. structure assoc'd w/ dull pain
    periaqueductal gray (in midbrain of brain stem)
  46. structure assoc'd w/ sharp pain
    cortex (cingulate, insular, somatosensory)
  47. - ligand-gated ion channel which selectively allows Cl- ions to flow into the cell when it is activated
    - made up of 5 subunits (w/ 15 subtypes) in 14 different combinations heterogeneously dist'd throughout the brain
    GABAA
  48. GABA R that is a G-protein coupled protein of which there are 2 subtypes
    GABAB

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