Term
| Name 3 cell bodies for dopamine: |
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Definition
Substantia Nigra
Pars Compacta
Ventral Tegmental Area |
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Term
| Name 5 projections of dopamine: |
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Definition
| Striatum, prefrontal cortex, limbic cortex, nucleus accumbens, amygdala |
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Term
| Name 3 catecholamines and what they are derived from: |
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Definition
Dopamine, Norepi, Epi
From TYROSINE |
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Term
| What are the 2 indolamines and what are they derived from? |
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Definition
Serotonin (5-HT)
Melatonin
From TRYPTOPHAN |
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Term
| What is histamine derived from? |
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Definition
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Term
| In Parkinsons disease, what cells from what area are missing? |
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Definition
| Pars compacta from pigmented substantia nigra |
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Term
| Why is MPTP toxic/why does it cause Parkinson's disease? |
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Definition
It passes the blood brain barrier and can be oxidized by MAO to MPP+ which is taken up by dopamine cells-
MPP+ is a mitochondrial toxin that kills dopamine cells |
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Term
| How can MPTP damage be prevented? |
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Definition
| MAO-Inhibitors and dopamine reuptake blockers |
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Term
| What are the classical symptoms of Parkinson's disease? |
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Definition
| Tremors, bradykinesia(SHUFFLING GAIT), rigidity, postural instability |
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Term
| What characterizes the neuropathology of Parkinson's disease? |
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Definition
| Lewy bodies- eosinophilic inclusion bodies filled with neurofilaments, glycoproteins, ubiquitin, and alpha-synuclein |
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Term
| How do we radiographically test for deficiency in substantia nigra cells? |
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Definition
| Radioactive tracer 6-fluoro-dopa on pet scanning shows decreased uptake of tracer if SN cells are lost |
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Term
What is the relationship of Parkinson's disease to dopamine?
What is the relationship of Schizophrenia to dopamine? |
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Definition
Parkinson's- too little dopamine
Schizophrenia- too much dopamine |
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Term
| In Parkinson's disease, what motor initiation pathway is not working? |
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Definition
MESOSTRIATAL PATHWAY NOT FUNCTIONING
-too little dopamine |
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Term
| What causes mesolimbic cortical dementia? |
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Definition
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Term
| Schizophrenia is caused by overactivation of what system? |
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Definition
| Mesolimbic-> Ventral Tegmental Area to limbic (cingulate cortex) |
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Term
| Parkinson's disease is caused by the breakdown of what system? |
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Definition
Nigrostriatal- substantia nigra to the caudate and putamen
Also called mesostriatal |
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Term
| What is the difference between mesolimbic cortical dementia and schizophrenia? |
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Definition
In Schizophrenia, the mesolimbic system is overactivated
In mesolimbic cortical dementia, the cells of the pathway are destroyed |
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Term
| What pathway is responsible for motor initiation, the cognitive aspects of Parkinson's disease, and the negative symptoms of Schizophrenia? |
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Definition
| Mesocortical pathway- Ventral Tegmental Area to cortex |
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Term
| What are the two ultrashort projections of dopamine in the brain? |
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Definition
Retina (between plexiform layers)
Olfactory bulbs- periglomerular cells |
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Term
| What are the two intermediate-length projections of dopamine in the brain? |
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Definition
Hypothalamus- tuberhypophysial cells and incertohypothalamic neurons
Medula- medullary periventricular group |
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Term
| What enzyme fails in PKU? |
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Definition
| Phenyalalanine hydroxylase |
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Term
| Describe the pathway from phenylalanine to dopamine, including enzymes: |
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Definition
Phenylalanine- hydroxylated with phenylalanine hydroxylase to L-Tyrosine
L-Tyrosine hydroxylated with tyrosine hydroxylase to Dopa
Dopa decarboxylated by dopa decarboxylase to DOPAMINE |
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Term
| Melanocytes convert what precursor and require what cofactor? |
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Definition
Melanocytes convert L-Tyrosine to Melanin, and require Cu to do so
using tyrosine hydroxylase |
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Term
| What is the most common treatment for Parkinson's disease? |
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Definition
| L-dopa given with carbidopa |
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Term
| Why is carbidopa given with L-dopa? |
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Definition
| It blocks the conversion of L-dopa to Dopamine but does not cross the blood brain barrier, so it prevents the L-dopa->Dopamine conversion OUTSIDE of the brain |
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Term
| What is recerpine used to treat and how does it work? |
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Definition
Hypertension and sometimes psychosis
Inhibits uptake of Dopamine vesicles and causes decreased storage of dopamine
This causes Parkinsonian symptoms |
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Term
| Why is it important that the inside of dopamine vesicles is acidic? |
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Definition
This decreases the rate at which dopamine oxidizes and degrades
(also true of Norepi and Epi) |
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Term
| How are neurotransmitters taken up into vesicles? |
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Definition
| ATPase Proton pump, and a specific secondary active transport H+/Neurotransmitter antiporter unique to each neurotransmitter |
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Term
| What enzyme is the major player in dopamine metabolism? |
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Definition
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Term
| What enzyme is critical to the minor pathway (extracellular) of dopamine metabolism? |
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Definition
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Term
| What enzyme is inhibited by disulfram? |
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Definition
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Term
| What is the end result of dopamine metabolism? |
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Definition
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Term
| What are 3 strategies for treating Parkinson's disease? (Concepts) |
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Definition
1- increase synthesis of dopamine
2- block degradation of dopamine
3- give dopamine receptor agonists |
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Term
| What is given to increase the synthesis of dopamine? |
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Definition
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Term
| What drugs are given to block the degradation of dopamine? |
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Definition
MAO-I- Deprenyl, selegiline
COMT-I- Tolcapone, Entacapone |
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Term
| Why does reserpine induce the symptoms of Parkinson's? |
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Definition
| Inhibits dopamine storage |
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Term
| What drugs induce Parkinson's-like symptoms? |
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Definition
Reserpine- for hypertension
TYPICAL antipsychotics- these are dopamine receptor antagonists:
Chlorpromazine, Loxapine, Haloperidol |
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Term
| What is a major side effect of L-Dopa? |
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Definition
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Term
| What effect does amphetamine have on dopamine? |
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Definition
| INCREASE VESICULAR RELEASE OF DOPAMINE |
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Term
| What effects do cocaine and tricyclic antidepressants have on dopamine? |
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Definition
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Term
| REVIEW DIFFERENTIAL DIAGNOSIS FOR PARKINSON'S |
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Definition
| REVIEW DIFFERENTIAL DIAGNOSIS FOR PARKINSON'S |
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Term
| What dopamine receptors are excitatory and what do they do? |
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Definition
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Term
| What dopamine receptors are inhibitory and what do they do? |
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Definition
| D2, D3, D4- decrease cAMP |
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Term
| Most antipsychotics inhibit what type of dopamine receptor? |
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Definition
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Term
| What enzyme is activated by cAMP? |
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Definition
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Term
| How is cAMP produced? How is it degraded? |
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Definition
Adenylyl cyclase activation by G protein
Phosphodiesterase |
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Term
| How do G-alpha-S receptors work? |
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Definition
| Excitatory- increase the activity of adenylyl cyclase |
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Term
| How do G-alpha-I receptors work? |
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Definition
| Inhibitory- decrease the activity of adenylyl cyclase |
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Term
| What cells in the substantia nigra project dopamine releasing fibers via the nigrostriatal tract to the caudate and putamen (together=striatum)? |
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Definition
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Term
| If dopamine levels drop and Ach levels stay the same, this is similar to what condition? |
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Definition
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Term
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Definition
| An intermediate in dopamine breakdown that is a neurotoxin- may be a contributor to Parkinson's in L-DOPA treatment |
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Term
| What are the positive symptoms of schizoprenia? |
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Definition
| Hallucinations, delusions, bizarre behavior |
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Term
| What are the negative symptoms of schizophrenia? |
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Definition
| Social withdrawal, emotional blunting |
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Term
| What structures in the brain are notably enlarged in schizophrenics? |
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Definition
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Term
| What cells orientation is altered in schizophrenia? |
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Definition
| The orientation of hippocampal pyramidal cells, which affects the molecules involved in cell migration and adhesion during brain development |
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Term
| In the hyperdopaminergia hypothesis for schizophrenia, what receptors are elevated and excessively activated? |
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Definition
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Term
| What are the locations of the cell bodies for serotonin? |
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Definition
BRAINSTEM-Midbrain and pons- Raphe nuclei (midline)
Medial and dorsal Raphe |
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Term
| What are the main targets of serotonin? |
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Definition
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Term
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Definition
| It affects mood, sleep, and behavior |
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Term
| Where is melatonin produced and what does it do? |
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Definition
| Pineal gland; regulates endocrine rhythms |
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Term
| Both melatonin and serotonin are derived from what? |
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Definition
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Term
| What is the primary enzyme for the breakdown of serotonin? |
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Definition
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Term
| What type of drugs seem to calm schizophrenia, and what is their major side effect? |
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Definition
D2 receptor antagonists
Parkinsonian Symptoms |
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Term
| What is the mechanism of action of typical antipsychotic drugs? |
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Definition
Target D2 receptors but are not very selective, so also act on D1's, cholinergic and histaminergic receptors
PARKINSONIAN SIDE EFFECTS-decreased cognition and alertness |
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Term
| What is the mechanism of action of ATYPICAL antipsychotic drugs? |
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Definition
Inhibit 5-HT2 receptors- serotonin
Can also have Parkinsonian symptoms but are much better tolerated |
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Term
| What is the effect of MAO Inhibitors on serotonin? |
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Definition
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Term
| Which classes of serotonin receptors are inhibitory and which classes are excitatory? |
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Definition
5-HT1 and 5 are inhibitory
All others (2-7+) are excitatory |
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Term
| What are some functions of melatonin? |
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Definition
| Circadian rhythms, antioxidant protective against DNA damage |
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Term
| Where do we find the MT1 receptor for melatonin? |
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Definition
Pars tuberalis of the pituitary
Suprachiasmatic nuclei of the hypothalamus |
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Term
| Where do we find the MT2 receptor for melatonin? |
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Definition
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Term
| What are the locations of cell bodies for Norepinephrine? |
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Definition
| PONS- locus ceruleus and lateral tegmental area |
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Term
| Where are the main targets for norepinephrine? |
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Definition
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Term
| What are the effects of norepinephrine? |
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Definition
| Alertness, mood elevation |
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Term
| Postganglionic sypmpathetic neurons use what neurotransmitter? |
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Definition
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Term
| What enzyme converts dopamine to norepinephrine and what cofactor is required? |
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Definition
Dopamine Beta Hydroxylase
Vitamin C |
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Term
| What enzyme converts norepinephrine to epinephrine, what induces it, and what is the cofactor? |
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Definition
PNMT
Induced by glucocorticoids as part of the epinephrine stress response
SAM |
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Term
| What enzymes are involved in catecholamine catabolism and what are the final products? |
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Definition
Enzymes: MAO and COMT
Product is Vanillylmandelic Acid VMA |
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Term
| What effect does reserpine have on norepinephrine and dopamine? |
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Definition
| It blocks the uptake of both |
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Term
| What effect does amphetimine have on norepinephrine and dopamine? |
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Definition
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Term
| Release of norepinephrine and dopamine is dependent on what? |
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Definition
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Term
Alpha 1 receptors:
Prefer what neurotransmitter?
Do what?
Act on what? |
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Definition
Norepi>Epi EXCITATORY
Increase IP2 and DAG
Smooth muscle contraction and glucose release from liver |
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Term
Alpha 2 receptors:
Prefer what neurotransmitter?
Do what?
Act on what? |
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Definition
Epi>Norepi INHIBITORY
Decrease cAMP G-alpha-I
Decrease insulin release, increase glucagon- presynaptic autoreceptors |
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Term
Beta 1 receptors:
Prefer what neurotransmitter?
Do what?
Act on what? |
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Definition
Epi=Norepi EXCITATORY
Increase cAMP
CARDIAC |
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Term
Beta 2 receptors:
Prefer what neurotransmitter?
Do what?
Act on what? |
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Definition
Epi>>Norepi EXCITATORY
Increase cAMP
Wide SYMPATHETIC activity (bronchi)
G-alpha-S |
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Term
Beta 3 receptors:
Prefer what neurotransmitter?
Do what?
Act on what? |
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Definition
Norepi>Epi EXCITATORY
Increase cAMP
Lipolysis in adipose tissue |
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Term
| What are the locations of cell bodies for histamine? |
|
Definition
HYPOTHALAMUS- tuberomammillary nucleus
MIDBRAIN- reticular formation |
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Term
| What are the main targets of histamine? |
|
Definition
|
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Term
| What is the effect of histamine? |
|
Definition
|
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Term
| How is histamine synthesized from histidine? |
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Definition
ONE DECARBOXYLATION STEP
histidine decarboxylase |
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Term
| What is the effect of the H1 histamine receptors? |
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Definition
| EXCITATORY- increases IP3 and DAG |
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Term
| Most antihistamines for allergies block what receptors? |
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Definition
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Term
| What is the effect of blocking H1 receptors in the brain? |
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Definition
| SEDATION- loss of alertness |
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