Neurobiology Final Module 3 Flashcards
Schizophrenia is thought to related to abnormal _____ levels in the brain
dopamine
Dopamine (DA) is a _____ neurotransmitter
catecholamine
Dopamine relies on the availability of the precursor amino acid _____ which also contributes to the production of _____
tyrosine, norepinephrine (NE)
When there is a stress response the rates of catecholamine production _____
increase
Catecholamine production can be increased by administering precursors such as _____ or _____
tyrosine, L-DOPA
Administering tyrosine when there is increased _____ or stress improves working memory
cognitive demand
vesicular monoamine transporter (VMAT) 1 is found in the
adrenal medulla
vesicular monoamine transporter (VMAT) 2 is found in the
brain
Depressive symptoms develop when catecholamine levels _____
drop
drugs such as _____ and _____ cause catecholamines to be released without depolarization of the neuron
amphetamines; methamphetamines
catecholamine levels are controlled through _____ and _____
metabolism; synaptic reuptake
reuptake occurs through _____ which return the neurotransmitter to the terminal for either recycling or breakdown
transporter proteins
_____ block transporters for both NE and serotonin (5-HT)
tricyclic antidepressants
_____ blocks transporters for all the monoamine transmitters
cocaine
MAO-A metabolizes _____
NE
MAO-B breaks down _____
dopamine (DA)
_____ includes the extrapyramidal system and regulates motor function
substantia nigra
deficiency in the basal ganglia results in _____ and _____
akathisia (restlessness), dystonia (involuntray muscle spasms)
_____ in the substantia nigra and the dorsal striata induces:
hyperkinetic movements
This pathway includes the reward system and regulates motivation and pleasure
ventral tegmental area (VTA) branching off to limbic system (nucleus accumbens, amygdala, and hippocampus)
Aggression and positive symptoms such as hallucinations and delusion result from _____ in the _____
DA hyperactivity, mesolimbic pathway
controls executive function and cognition
dorsolateral prefrontal cortex (DLPFC)
regulates affect and emotions
ventromedial prefrontal cortex (VMPFC)
loss of motivation, anhedonia, lack of pleasure
negative symptoms
What are the two most common metabotropic DA receptor subtypes in the brain
D1 and D2
Nearly all current antipsychotics are:
D2 receptor antagonists
_____ are both auto receptors and postsynaptic receptors
D2 receptors
high doses of DA antagonist drugs induce _____
catalepsy (lack of spontaneous movement)
A common D2 receptor blocker associated with catalepsy is:
haloperidol
Long term dosage of D2 receptor antagonists lead to the development of :
dopamine supersensitivity
when there is a lack of a neurotransmitter, neurons will increase the number of receptors called:
receptor upregulation
What is a hallmark characteristic of schizophrenia
disturbed thought
hallucinations, delusions, disorganized speech, bizarre thought patterns, and unusual behaviors
positive symptoms
positive symptoms respond well to meds that:
block D2 receptors
alogia, flattened affect, avolition, social withdrawal, and anhedonia
negative symptoms
impaired working memory, loss of executive function, and impaired attention:
cognitive symptoms
symptoms most resistant to antipsychotics are:
negative and cognitive
common structural changes r/t schizophrenia include (4)
reduced volume in basal ganglia
cerebral atrophy
ventricular enlargement
reduced volume in hippocampus and temporal/frontal cortices
The most common consistent change in schizophrenia is:
reduced PFC function r/t decreased blood flow
During the first episode of schizophrenia, _____ are elevated and _____ are decreased
pro inflammatory mediators, anti-inflammatory cytokines
Immune disorders such as diabetes, RA, and Crohn’s _____ the risk of schizophrenia
increase
phenothiazines (chlorpromazine) and butyrophenones (haloperidol)
classic neuroleptics
antagonism of DA transmission through competitive blockade of receptors or inhibiting the release of DA
classic neuroleptics
Antipsychotics bind to the following receptors (3):
serotonin
adrenergic
histamine
How can you reduce parkinsonism symptoms?
combine dopamine blockade with an anticholinergic such as benztropine
muscle rigidity, fever, altered consciousness, and autonomic lability
neuroleptic malignant syndrome
what is treatment for NMS
calcium channel blockade (dantrolene)
a postsynaptic receptor with excitatory function that stimulates glutamate and GABA release which regulates DA release
5-HT2A
Blocking 5-HT2A stimulates:
DA release
regulates both DA and NE at the postsynaptic receptor
5-HT2C
stimulating 5-HT2C receptor leads to:
significant weight loss
blocking 5-HT2C receptor leads to:
increased DA and NE in the PFC improving cognition
List the 2nd generation antipsychotics that block 5-HT2C and bind to 5-HT2A (4)
clozapine
olanzapine
quetiapine
asenapine
List the 2nd generation antipsychotic “dones” (4):
risperidone
ziprasidone
paliperidone
lurasidone
List the 2nd generation antipsychotics that are characterized by partial 5-HT1A agonism and have the lowest cardiometabolic risks (3)
cariprazine
aripoprazole
brexpiprazole
What is the gold standard for antipsychotics
Clozapine
What risk is associated with clozapine
agranulocytosis
What antipsychotic has the highest risk for cardiometabolic consequences
Olanzapine
Becomes more like a classical neuroleptic at higher doses and approved for symptoms of irritability for patients with autism spectrum disorder
risperidone
least risk for weight gain and metabolic complications, less sedating, must be taken with 500 calorie meal for absorption
ziprasidone
