Synapses, receptors and drugs, brain orientation

• Neurotransmitter types


  • Amino acids: glutamate, GABA, glycine, aspartate
  • Monoamines: dopamine, serotonin, noradrenaline
  • Peptides: opioids, substance P, endorphins
  • Others: acetylcholine, anandamide, oxytocin

  
• neurotransmitter actions

  • many brain regions mostly use one transmitter
  • dopamine
  • associated with reward (nucleus accumbens) and movement (substance nigra)
  • serotonin (5-HT)
  • regulates sleep, mood (raphe nuclei, hippocampus)
  • acetylcholine
  • movement (neuromuscular junction)
• chemical interactions

  • neurotransmitter bind to receptors
  • affinity: how strongly chemical binds to receptor
  • efficacy: how strongly chemical activates the receptor
  • other chemicals can bind to the same receptors
  • agonists: mimic the action of neurotransmitter
  • antagonists: block the neurotransmitter from binding; do not activate the receptor
• possible drug mechanisms (selected)

  • bind to postsynaptic receptors
  • agonists or antagonists; varying affinities and efficacies
  • affect neurotransmitter synthesis
  • increase/decrease amount of precursor
  • degrade transmitter
  • cause vesicle leakage
  • break down transmitter in synaptic cleft
  • block transmitter reuptake (SSRI)
• receptor types

  • ionotropic/metabotropic
  • excitatory/ inhibitory
  • often consists of subunits
  • may be unevenly distributed in brain regions (dopamine D1, D2)
  • different subunits may bind slightly different drugs (GABAa receptors)
• GABA receptors

  • GABA is the most common inhibitory neurotransmitter
  • has 2 different receptors:
  • GABAa receptors:
  • ionotropic
  • Allow Cl- ions to enter the postsynaptic cell when open
  • subtype (GABAc) made all of the p subunits (in retina)
  • GABAb receptors:
  • metabotropic
  • mediate long-term inhibitory effects
  • proteins affected eventually open K+ channels
• Distribution of dopamine receptor subtypes

  • Cortex: D1, D2, D4, D5
  • dorsal striatum: D1, D2, D5
  • Nucl. acc. : D1, D2, D3, D5
  • GP: D4
  • hypothalamus: D1, D2, D4, D5
  • SN: D2, D3, D5
  • VTA: D2, D3, D5
  • hippocampus: D1, D2, D4, D5
• long-term effects

  • Receptors become less/more sensitive
  • nicotine: increase dopamine release (like cocaine)
  • long term exposure sensitizes receptors
  • morphine; high affinity agonist of opioid receptors
  • receptors become less sensitive, are decoupled from their G-proteins, or are sucked into the cell
  • Dosage-dependent effects
  • MDMA (E) increase release of dopamine at low doses, and serotonin as well at high doses
  • alcohol at increasing doses; euphoria, lethargy, memory loss, confusion, coma
• Selective serotonin reuptake inhibitors (SSRI)


  • Prevent reuptake of serotonin
  • More serotonin left in synaptic cleft for longer
  • Over-stimulation of postsynaptic cells
  • Function as antidepressants (Prozac, Paxil, Zoloft)
• Retrograde mesengers 


  • THC: Binds to cannabinoid receptors (for anandamide) on the presynaptic neuron
  • Prevents release of (further) neurotransmitter
• Contenxtual effects

  • Heroin (=morphine, fentanyl); Opioid receptor agonist
  • long term, cells decrease number of receptors
  • tolerance and withdrawal effects
  • taking in a new place can cause overdose(conditioned tolerance)
• Brain orientation 


  Directions:

  • Dorsal: (towards back) top
  • ventral: (towards belly) bottom
  • anterior: front
  • posterior: back
  • medial: middle
  • lateral: side

  planes:

  • horizontal
  • saggital: down the nose (down the middle in hotdog way)
  • coronal: down the ears (down the middle in the hamburger way)
• Tissue

  • Brain has 2 kind of matter
  • grey matter: somas, dendrites (in open)
  • white matter: axons, bundle of axons (in crevices)
• Peripheral nervous system (PNS)

  • everything except brain and spinal cord
  • PNS branches into somatic and autonomic
  • Somatic: transmits messages to/from brain, sensory division
  • autonomic: operates automatically, connects rest of body to spinal cord, branches into sympathetic and parasympathetic
  • sympathetic: increased activation, "fight or flight"
  • parasympathetic: decreased activation, "rest and digest"
• Central Nervous system (CNS)

  • consists of spinal cord and brain
  • coordinates and controls movement (mostly)