ACh
Immunocytochemie adhv choline-acetyltransferase of acetylcholinesterase, clear/translucent vesicles
Receptoren:
- Nicotine-R: ionotroop, NN,M, 2 ionen nodig voor opening van receptorkanaal Na+ en K+ stijgt, perifere
cholinesterase inhibitor pyridostigmine bij myasthenia gravis
- Muscarine-R: metabotroop, M1-5, GPCR, direct of via 2de boodschapper, atropine als antagonist
o M1,3,5: stimulatie PLC Ca2+ stijgt
o M2,4: inh. AC K+ stijgt
o Farmaca bij Alzheimer: Memantine = inh., centrale cholinesterase inhibitor tacrine
- Postsyn. Na+-, K+-, Ca2+-stroom verandert exciteerbaarheid verandert, AHP door activatie K +(Ca2+)-kanalen
Formatio reticularis met RAS met nucleus basalis van Meynert cortex (diffuus over 6 lagen), thalamus, amygdala,
hypothalamus
- D1-fam: D1,5: stimulatie AC, activeren Ca2+-signalisatie, exc.
- D2-fam: inh. AC, onderdrukken Ca2+-signalisatie via sluiting Ca2+-kanalen, meer K+
o D2: autoreceptor, minder availability bij farmaca
Parkinson en schizofrenie en bij novelty seeking
personality, in SNc en striatum
o D3: meer availability bij schizofrenie en
verslaving, in NA en hypothalamus
o D4: ADHD, in MS en MC en frontale cortex
Tubero-infundibulair systeem: inh. prolactinevrijstelling
(lactatie), reward learning, impulse control diseases zoals kleptomanie en pyromanie
Parkinson: nigrostriatale baan: SNc striatum, 8 hypothesen, L-Dopa over BBB endotheel via L1 samen met perifere
decarboxylase remmer zoals benserazide, MAO-B inhibitoren zoals selegiline
Schizofrenie: onderactiviteit mesocorticale en overactiviteit mesolimbische baan: MC PFC en limbische cortex
neg. en pos. symptomen
Verslaving: overactiviteit VTANA baan, opiaten: μ-R op GABAerge neuronen disinh., alcohol: disinh., nicotine:
stimulatie DOPerge neuronen, cannabinoïden: inh. GABAerge neuronen thv NAc, cocaïne en amfetamine remmen
re-uptake DOP, mediale PFC, amygdala en hippocampus sturen exc. Gluerge neuronen nr NA, deel hedonisch
systeem(voortzetting)
ADHD: hypoactiviteit DOP
Afbraak door MAO presyn en in gliacellen: Selegiline inhibeert
DAT=transporter voor presyn re-uptake: geremd door rilatine en cocaïne, amfetamine kan hier ook door en
stimuleert dan DOP vrijstelling psychostimulantia verhogen c DOP in synaps
5-HT
<tryptofaan AA
Verwijderd uit synaps door re-uptake en afbraak door MAO: immuunhistochemie
Nuclei raphes: rostraal en caudaal volledig CZS
Synaptic cradle: ook astrocyten en microgliacellen, ~noradrenerge synaps
Antidepressiva: re-uptake inh.: Prozac=fluoxetine of MAO inh.
Onderdrukt REM
Depressie: lage 5-HIAA in CSF: afbraakproduct, ook rol NOR en groeifactor voor neuronen, stress Glu
excitotoxiciteit en verhoogd cortisol neuronale apoptose
2
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