Flashcards in Lecture 16 Deck (23):
Is there a genetic component to schizophrenia?
YES - strong
What is the dopamine hypothesis?
Anti-psychotics work as dopamine antagonists
Block dopamine binding at D2 receptor
- Amount of D2 receptor changes how well these drugs work
Means pituitary won't seen any dopamine - ↑prolactin
When you're on anti-psychotics, is your HVA ↑↓?
↑dopamine circulating because receptors being blocked by antagonists
How does dopamine signaling change in schizophrenia?
MORE dopamine singaling
This is why D2 blockers work - decrease the number of signals getting through - normalize levels
How does the brain respond to antipsychotics given for schizophrenia?
↑ # dopamine receptors
Body's natural response to these drugs is to upregulate the receptor
What are the major dopamine pathways in the brain? Where does it start/end?
Substantia nigra --> forebrain/limbic regions
Substantia nigra --> striatum, connects basal ganglia
Are GABA and glycine excitatory or inhibitory NTs?
Are glutamic and aspartic acid excitatory or inhibitory NTs?
Describe the GABA/glycine receptor.
Same as ACh - 4 transmem domains, assembles as pentamer
Receptor = channel
BUT is lined with positive charges for ANION selectivity
Describe the response when GABA/glycine binds the receptor.
Move Cl- through the receptor pore
Inhibitory response because makes the membrane more negative - harder to reach threshold
Where do you find GABA: brain vs spinal cord? Glycine: brain vs spinal cord?
GABA - brain, especially substantia nigra and striatum
Glycine - spinal cord
Describe the GABA neuronal pathway. What disease is this pathway linked to?
Cell bodies @ striatum
To substantia nigra
Links basal ganglia (coordination of motor movements)
Degenerates in Huntington's
Describe the glycine neuronal pathway. What disease is this pathway linked to?
Act as spinal cord interneurons between motor neurons (think biceps activated while inactivating triceps)
Knocked out by tetanus - spasm result
What drug increases the action of GABA?
- Allosteric binding site @ GABA receptor
Prolongs GABA response because ↑s receptor's affinity
Describe the 2 main glutamate receptors. What is their major role as excitatory NT receptors in the brain and spinal cord?
- Activated by AMPA
- Permeable to Na or Ca
- Activated by NMDA
- Permeable to Ca
Role: memory & learning
*Ca and Na are positive so push membrane towards threshold --> depolarization (excitatory role)*
What is NMDA?
Agonist of glutamic and asparatic acid
Describe the general structure of the glutamate receptors.
TETRAMER assembly (not like ACh)
Clam site = site of conformational change when bind
- Part of LARGE extracell domain
Why are glutamate and aspartate potentially neurotoxic? What drug can you use to counter this?
Swelling and neuronal death
USE: NMDA antagonists
Where in the brain do you find NMDA receptors?
Describe Huntington's pathology.
Unknown degeneration of GABA neurons --> leads to excess of excitatory NT release --> excessive activation of NMDA pathways
What might the NMDA receptor use as a second messenger? Describe its synthesis.
- arginine + NO synthase = NO
Activates guanylyl cylase in neighboring cells to ↑cGMP
Where is NO found in the brain?
Cerebellum - granule & basket cells