Dopamine Systems - 29 Flashcards
What is Dopamine?
A Monoamine neurotransmitter
What does dopamine do?
Translates thoughts into action : decision making, goal directed behavior, movement : affects mood
What are the pathways of the brand for Dopamine?
Mesocortial, Mesolithic, Nigrostriatal, Tuberoinfundibular, Chemoreceptors trigger zone
What is the Mesocortical pathway in control of?
Cognition
What is the Mesolithic pathway in control of?
Integration of emotional responses; “complex reward-oriented behavior”
What is the Nigrostriatal pathway in control of?
Motor; planning and execution; “automated behaviors”
What is the Tuberoinfundibular pathway in control of?
Inhibits prolactin release and regulates growth hormone release from the pituitary
What is the chemoreceptors trigger zone in control of?
Gag/vomit reflex - nausea
Where is dopamine synthesized?
In the pre-synaptic terminals
Where is dopamine stored?
In vesicles of the pre-synaptic terminals
What controls the release of dopamine?
Action potentials
What kind of receptors are dopamine receptors?
GPCRs
Are dopamine receptors excitatory or inhibitory?
They can be either
What does the dopamine transporter do?
Removes dopamine from the synapse for repackaging/use
What are the molecules of the dopamine pathway?
Tyrosine, L-DOPA, Dopamine, DOPAC, HVA
What are the enzymes of the Dopamine pathway?
Tyrosine hydroxylase, DOPA Decarboxylase, MAO, COMT
What are the steps of the Dopamine pathway?
Tyrosine (Tyrosine Hydroxylase) L-DOPA (DOPA Decarboxylase) Dopamine (MAO) DOPAC (COMT) HVA
What happens if you delete the Dopamine Transporter?
You’d have more dopamine in the clefts/increased motor activity
What is Parkinson’s Disease?
A neurodegenerative disease resulting from a loss of dopamine neurons
What would you notice in a brain with Parkinson’s?
Lack of pigmentation in the Substantia Nigra (no oxidation of dopamine)
What motor features do Parkinson’s Disease patients have?
“TRAP” : Tremor (when at rest) : Rigidity : A(Brady)kinesia (absense of movement) : Postural instability :::: Also, trouble swallowing, difficulty initiating walking, “masked” facial expressions
Does Parkinson’s Disease decrease life expectancy?
NO, but increased accidental death
What are some NON-motor symptoms of Parkinson’s?
Depression/anxiety, pain, speech/swallowing problems, sleep disturbances, autonomic symptoms
What are examples of “autonomic symptoms” of Parkinson’s?
Constipation, orthostasis (lightheaded upon standing), sexual dysfunction, sweating abnormalities
Who gets Parkinson’s?
1-2% over 65, 3-5% over 85; ~4% <50yrs
Is there an increased risk of PD in relatives?
Slight increase in first-degree relatives
T/F All cases of Parkinson’s Disease are related to an identified single gene
F - <10% of cases are related to an identified single gene
What are environmental causes of Parkinson’s?
pesticides, head injury, infection, MPTP, Manganese (may be viral/bacterial!!!)
What are some things that decrease the risk of Parkinson’s?
Smoking, and Caffeine
What are the genetic causes of Parkinson’s Disease?
Increased risk in family members, multiple genetic risk factors
How do we treat Parkinson’s?
Treat the symptoms. Improve function/QoF. Replace brain dopamine (give L-Dopa)
What can you do to slow/reverse the effects of Parkinson’s?
There is no known treatment to slow or reverse the progression of Parkinson’s
What things can PD treatment help with?
Treat bradykinesia/rigidity, tremor, sometimes postural/gait treated
What drug is given to replace Dopamine?
L-DOPA (Levodopa)
Why cant we just give Dopamine instead of the precursor?
Dopamine will be broken down in the periphery before getting into the brain.
What treatments are there that are aimed at the dopamine system?
Replace Dopamine : Enhance Dopamine : Dopamine receptor agonists
How do you enhance Dopamine?
Prevent the conversion of L-DOPA to Dopamine in the periphery (Dopamine cant pass BBB)
What drugs “enhance dopamine”?
Carbidopa, Entacapone, Rasagiline, Selegiline, and Low dose cocaine
What is the name for the drug that combines Carbidopa and Levodopa? Why would you do this?
Sinemet; Carbidopa stops the breakdown of L-DOPA in the periphery, and Levodopa IS L-DOPA
What is an example of a dopamine receptor agonist?
Pramipexole
What effects does Levodopa have?
CNS effects: Reduced bradykinesia/rigidity, antidepressant ::: Endocrine effects: decreased prolactin release ::: GI: Nausea/vomiting (take w/ food) ::: CARDIOVASCULAR SYSTEM: Orthostatic hypotension, cardiac stimulation
How do the motor complication of Parkinson’s progress from early to advanced?
Early: Long-duration of L-DOPA effect with little dyskinesias ::: Moderate: Short-duration of effect with some dyskinesias ::: Advanced: Short-duration with consistent dyskinesias
What are some of the Pros and Cons to using a Dopamine Receptor Agonist?
Lasts longer than Levodopa (smooths wearing off feeling when used together); More side effects
What are some side effects of Dopamine Receptor Agonists?
Sleep attacks, Impulse Control Disorders (compulsive gambling…)
What are som “other Pharmacological approaches” to PD?
Benztropine (Cogentin) and Amantadine (Symmetrel)
What is Benztropine?
Cogentin; Muscarinic antagonist : cognitive side effects/fatigue
What is Amantadine?
Symmetrel; antiviral; increases dopamine release/reduces reuptake
What is the most modern treatment for Parkinson’s? When is it used?
Deep Brain Stimulation : when pharmacological therapies fail
Contraindications for Deep Brain Stimulation:
Cognitive impairment; postural instability; uncontrolled depression
What is Huntington’s Disease?
Neurodegenerative disorder: Genetic disease
What inheritance is there for Huntington’s?
Autosomal dominant: Trinucleotide repeat on Chromosome 4
When does Huntington’s onset?
Between 20-40
What are some characteristics of Huntington’s?
Demonstrates anticipation; Psychiatric disturbances (1st); Chorea; dystonia; dementia/DEATH
What is Chorea?
Jerky/involuntary movements of the shoulder/hips/face
What are some psychiatric symptoms of Huntington’s?
Depression, psychosis, bipolar
How do we treat Huntington’s?
Treat Chorea with Dopamine ANTAGONISTS ::: Treat bradykinesia/rigidity with Dopamine AGONISTS
What are the main dental implication of Huntington’s and Parkinson’s?
Exam difficulty, hygiene, and drug interactions
