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psychopharm exam 2
| Term | Definition |
|---|---|
| catecholamine | -dopamine, epinephrine, and norepinephrine are main 3 types - are neurotransmitters and hormones produced in response to stress |
| tyrosine | -amino acid - made from proteins we eat -converted into DOPA |
| how is tyrosine converted to DOPA | -tyrosine, after being synthesized is transported to brain via general blood circulation - tyrosine hydroxylase converts tyrosine to DOPA |
| how is DOPA converted into DOPAMINE | via AADC (amino acid decarboxylase) |
| amino acid decarboxylase | converts DOPA into dopamine |
| what regulates Dopamine synthesis | firing rate of dopamine neurons -ex: if a dopamine pathway isn’t active, the neuron doesn’t need to synthesize dopamine |
| more info on dopamine synthesis regulation | - is a feedback loop on tyrosine (nip it in the bud if its too much) - inhibits or stimulates tyrosine -high activity: ^ tyrosine hydroxylase -dopamine synthesis is self regulated *this is more of a transient regulation, not an immediate order |
| drugs that block DA synthesis tell us about | the role of dopamine in behavior |
| AMPT-alpha methyl p tyrosine | blocks tyrosine hydroxylase |
| where on the neuron can dopamine act | the terminal button but ALSO in other places! fun fact |
| why does dopamine need to be stored in vesicles | because there are intracellular enzymes that would otherwise break it down |
| VMAT2 | the protein that transports dopamine into the vesicles after it has been synthesized *VMAT1 is in the adrenal medulla |
| alternate method of dopamine release that is not the traditional model | dopamine release from varicosities along the axon |
| traditional “fast” release | axodendritic and axosomatic synapses |
| varicosical release | there are varicosities (swellings) along the axon that contain synaptic vesicles which contain dopamine |
| approximately ___% of dopamine neurons have these varicosities and ___% of those actually release dopamine from those varicosities | 70, 30 |
| why do some varicosities with dopamine not release the dopamine | they dont have active zones needed |
| dopamine can be recycled via | transporter proteins |
| ritalin and adderal | evidence for dopamine transport inhibition (because remember transporter proteins are what recycle DA in reuptake; so ritalin and adderal block DA reuptake) block dopamine transporters used to treat ADHD also enhance DA and norepinephrine (Ne) release |
| how many ways/through how many mechanisms are auto receptors able to clear dopamine/ inhibit DA release | 2 -second messengers -voltage gated potassium channels |
| second messenger auto receptor systems | second messengers can be sent to block calcium (Ca2+) channels this prevents exocytosis, which in turn inhibits DA activity |
| voltage gated potassium channel auto receptors | opening voltage gated potassium channels along the axon leads to a K+ efflux (decrease) and this in turn prevents the action potential from b being propagated down the axon and from reaching axon terminal |
| types of enzymes that can inactivate dopamine | Monoamine Oxidase (MAO) (intracellular) COMT (intracellular and extracellular and peripherally [PNS, especially in liver]) *both can be problematic because they break down DA and DA precursers (COMT breaks down DOPA in liver) |
| parkinson’s treatment | lack of dopamine why DOPA is administered as symptom treatment |
| L DOPA | levadopa used in parkinson’s treatment alongside COMT inhibitor or another enzyme inhibitor dopamine precurser |
| ascending dopamine pathways | 3 of them -nigrostriatal pathway -mesolimbic pathway -mesocortical pathway |
| midbrain | at top of brain stem |
| dorsal striatum | striatum is part of the basal ganglia! consists of 2 components: caudate putamen the dorsal striatum is just these 2 components put together—that’s it |
| substantia nigra | a small brain structure in the midbrain that plays a critical role in motor movement, reward functions, and other brain processes where cell bodies are? |
| caudate | part of dorsal striatum supports body position/posture |
| putamen | controls/supports motor learning contains globus pallidus |
| key behaviors that the nigrostriatal pathway support | voluntary movement |
| globus pallidus | supports proprioception (knowing where our body is in space/the sense of body position and movement) |
| basal ganglia | voluntary movement and motor control and other behaviors |
| substantia nigra in parkinson’s | we see a degradation of the substantia nigra in parkinson’s disease -aka degradation of the cell bodies of dopamine neurons whose cell bodies are in this area (because remember this area is where the somas are) -we see under activation of these neurons |
| limbic region/system | land of misfit toys includes hypothalamus, amygdala, thalamus…weird combo |
| ventral tagmental area | a midbrain structure that plays a role in reward, motivation, and other functions *both mesolimbic and mesocortical pathways originate here; axon bundles split eventually |
| nucleus accumbens | part of limbic system neural interface between motivation and action, playing a key role on feeding, sexual, reward, stress-related, drug self-administration behaviors, etc. |
| amygdala | major processing center for emotions, memories, learning and senses learning anf memory =- reinforcement and reward that mesolimbic area supports |
| hippocampus | learning, memory, and spatial navigation learning=reinforcement, reward that mesolimbic area does |
| key behaviors mesolimbic pathway supports | behavioral arousal/stimulation/activation/motivation perception of pleasure reward and reinforcement (VTA) perception of pain/aversive stimuli (relies on adjacent mesolimbic pathway (adjacent to pleasure one i think)) (causes blurred lines between) |
| dysfunction in mesolimbic system underlies | ADHD Depression Addiction |
| key behaviors that the mesocortical pathway underly | identification of novelty in our environment -we pay ATTENTION to novelty -executive function -reason drug related cues induce craving in addicts—its because the drug draws attention -tightly intertwined with COMT |
| firing rate of DA neurons in the mesocortical pathway | dependent on the rate of COMT breaking down DA more/higher COMT breakdown rate=lower firing rate of DA neurons firing rate goes down as COMT goes up because when firing occurs, the cell expends DA—cell stops firing to stop releasing DA, save it up |
| met allele | codes for slower COMT functioning; in people with homozygous met, COMT is slow to break down DA and therefore have better/higher cognitive functioning |
| val allele | codes for faster COMT functioning; in people with homozygous val, rapid DA breakdown by COMT; therefore have lower cognitive functioning -people with homozygous val their frontal lobe is highly functioning (hypofrontaslity?) and COMT working too hard |
| val met | variations of an allele that code for synthesis of COMT |
| val-met allele as it relates to schizophrenia | people with schizophrenia tend to have a higher proportion of val-val (val homozygous) alleles |
| cannula | held by a stereotaxic instrument allows for targeted/direct somatic manipulation stays in the area for multiple administrations |
| stereotaxic instrument tells you | 1. where to place an electrode (which artificially and electrically stimulates a bundle/area of cells in the brain) 2. can be used to ablate or lesion a portion of the brain and seeing a change tells us what that area does |
| morris water maze | shows us spatial memory and learning of a subject |
| open field test | tests anxiety and fear, could potentially induce it |
| tail flick or shock test | measures pain tolerance |
| microdialasis | use a cannula to extract fluid (rather than inject) and then determine neurotransmitter density/concentration based off of that fluid |
| functional magnetic resonance imaging (fMRI) | shows blood flow to brain parts idea is that active brain areas use more oxygen so need more blood flora there to replenish likely has a better spatial and temporal |
| transcranial magnetic stimulation (TMS) | allows you to transiently manipulate physical structures the magnetic pulse temporarily stops brain function in the area |
| positron emission tomography (PET) | a tracer (radioactive?) is consumed and binds to glucose receptors, follows em |
| electroencephalography (eeg) | measures different states of arousal, general cognition//measures neuronal activity/signals great temporal, poor spatial resolution -event related potentials (ERPs) can be taken from this; within the eeg, infinite cognitive operations |
| CT scan (computed tomography) | used clinically cheaper than MRI -multiple x rays taken to identify differences in tissue density |
| magnetic resonance imaging (MRI) | used more in research than clinically because its expensive measures distribution of H2O in nervous system alignment of protons after bursts of radio waves |
| diffuser tensor imaging | tract looks at white matter structural integrity looks at diffusion of water around axons healthy tracts will have water diffuse/move around it |
| soup method | method of measuring affinity of ligand binding to receptors -dissolve brain tissue in liquid (homogenate) when you take a sample you can see the denisity of ligand binding at that tissue ex: radioligand binding |
| slice method | method of measuring affinity of ligand binding to receptors -can understand density and distribution (WHERE it actually is in the brain) -ex: autoradiography ; bathed in fluid with radio ligands, see where they bind |
| d1 receptor | locomotion -we know this because d1 agonists enhance locomotion |
| d2 receptor | |
| d3 receptor | |
| haloperidol | D2/D3 antagonist relativley effective in reducing delusions, hallucinations (positive schizophrenia symptoms) ^can be used to treat schizophrenia positive sympotoms |
| positive symptoms | presence of atypical behavior |
| negative symptoms | absence of normal behavior ex: disorganized speech and thinking, attention issues, more cognitive functioning stuff , flat affect, speech poverty characterized by under dopamine activation in mesocortical areas |
| what makes schizophrenia interesting scientifically | it is characterized by both too much and too little dopamine |
| cholinesterase inhibitors | used to treat negative symptoms *most traditional treatment only targets positive Sx inhibit enzymes that break down acetylcholine initially used in dementia and alzheimers NOT VERY EFFECTIVE IN TREATING NEGATIVE SX OF SCHIZOPBRENIA |
| acetylcholine | plays a role in memory, learning, attention, arousal and involuntary muscle movement. |
| cariprozene | used to treat negative Sx of schizophrenia is a partial D2/D3 agonist increases DA in hypofunctioning mesocortical networks , which treats negative Sx decreases DA transmission at hyperactive D2/D3 receptors (mesolimbic) relative to DA NT itself |
| partial agonist | has properties of both agonists and antagonists partially activate receptors activate receptors less than a full agonist or dopamine would |
| receptor regulation is what kind of tolerance | psychodynamic |
| 2 ways that receptor regulation can happen through | 1. changes in receptor sensitivity through chronic drug use 2. repeated exposure to an agonist |
| receptor regulation (why it happens and how it affects the person) | the body does downregulation (reduces # of receptors in attempt to reduce effect of drug) this leads to behavioral consequences; people just take more of the drug to combat this |
| how does repeated exposure to an antagonist affect a person neurologically and behaviorally | produces upregulation in body:more receptors added for NT to bind to this can produce behavioral super sensitivity—an increased response to other drugs that affect the same NT/receptors *this can be an issue if the next drug is an agonist |
| in order for a drug to be addictive, it has to_____? | produce pleasure (pleasure is subjective) |
| punishment leads to what kind of learning | faster but less stable |
| self administration paradigm | used to measure reinforcing properties of a drug reinforcement of a drug is measured by how many lever presses an animal does -if the drug is highly reinforcing, |
| how can drugs be positive reinforcers | the drug itself is the reinforcer and the action; in taking a drug that makes you feel good, the reward is feeling good so you will do that action again to feel that feeling again: OPERANT CONDITIONING |
| what type of conditioning is used in the addiction/drug reward framework | operant reward, punishment, positive, negative |
| progressive ratio schedule | used to stop animal from overdosing during self admonistrationparadigm phases 1.continuous reinforcement phase 2.second phase |
| issue with the self administration paradigm | if the animal keeps pressing the lever, eventually it will pass out from too much drug to fix this, we use a progressive ratio schedule, which increases the number of times a rodent has to press the lever before it gets the drug: |
| breakpoint | measures when its too many lever presses to get the drug; risks finally outweigh reward—the breakpoint ratio in which the rodent stops responding;how many times will they press the lever without getting the drug? effort to press lever outweighs reward |
| what is the risk of abuse for a drug with a high breakpoint | high - they are willing to give up a lot before they finally stop taking the drug money, relationships, etc |
| continuous reinforcement phase | simple lever press=drug just teaching them that^ no ratio or timing or anything |
| second phase of progressive ratio schedule | progressively increase fixed ratio schedule im going to deliver drug every __ amount of lever presses -you increase x until rodent reaches breakpoint— when they stop responding/lever pressing |
| do consequences reduce drug use? | no there is too big of a delayed temportal relationship between drug administration and consequences (days, weeks, months) what WOULD work is a short time, like 3 seconds even if we know it is bad, there is no actual brain learning taking place |
| theory as to why addictions continue | other than the benefits of the drug itself,,, to avoid withdrawal |
| types of tolerance | behavioral, metabolic, psychodynamic |
| behavioral tolerance | context specific tolerance the one that has to do with overdosing in a new environment only |
| what produces drug cravings? | cues -they also initiate metabolism—get the body ready to take on drug |
| metabolic tolerance | over time we get better at clearing a drug which reduces its bioavailability *an example of. this is the body producing more enzymes to break down the NT, in the liver for example (like COMT for dopamine!) |
| psychodynamic tolerance | receptor based repeated use of an antagonist causes upregulation of receptors at synapses repeated use of agonist causes downregulation of receptors body tries to work with what it has to get amount of drug it wants |
| where does degeneration start in stage 1 parkinsons | vagus nerve and anterior olfactory bulbs (underlies early loss of smell) generally in the medulla/brainstem, spreads through brainstem? maybe? |
| vagus nerve degeneration | occurs in medulla (dorsal motor nucleus of medulla) |
| lewy bodies | -abnormal clusters of alpha synuclein, which naturally occurs in body and itself is not dysfunctional -result from cellular breakdown - a sign of cell death/breakdown originate in brainstem |
| what does alpha synuclein usually do | needed for vesicle docking -when they are abnormal (lewy bodies), docking goes bad |
| is parkinson’s detected in stage 1? | no, because the symptoms aren’t parkinson’s specific |
| symptoms in stage 1 parkinsons | constipation extreme levels of fatigue endocrine secretion of an oily substance which produces an odor in 60% of cases |
| vagus nerve | |
| degeneration in stage 2 parkinson’s | we see degeneration in 2 hubs of pathways in the midbrain/pons (brain stem) 1.raphe nucleus 2. locus coeruleus |
| raphe nucleus | seratonin? primary hub has to do with sleep, wake cycle, and cognition degeneration of this correlates with mood and sleep based symptoms of stage 2 parkinson’s |
| locus coeruleus | modulate arousal states and adaptive behavior and stress response degradation of this correlates with mood and affect and sleep Sx in stage 2 parkinson’s |
| when do we see degradation of substantia nigra | stage 3 parkinson’s; this is the main thing we see in parkinson’s |
| stage 3 breakdown | lewy body accumulation in nigrosriatal pathway where dopamine gets from substantia nigra to basal ganglia cell bodies of that tract that lie in the substantia nigra and degraded |
| substantia nigra function | used to translate motivation to move to actual movement |
| lewy body effect in stage 3 | it causes an imbalance of IPSP and EPSPs in the nigrostriatal pathway |
| MPTP | (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) neurotoxin that stays outside of the cell in a healthy NS its oxidize state MPP+ destroys cells in mitochondrial dysfunction hypothesis of parkinson’s |
| what provides MPTP | MAO (remember it breaks down monoamines like 5HT) both MAO and MPTP are normal in the NS |
| where does disaster strike with MPTP in mitochondrial dysfunction hypothesis | it enters the cell (substantia nigra cells) through DA transporter proteins this is not supposed to happen it gets oxidized into MPP+, which damages cells from here, it accumulates in the mitochondria |
| can dopamine pass B.B.B.? | no but dopa can! |
| what happens when MPP+ accumulates in the mitochondria of a substantia nigra cell | energy production decreases we beleive this is what underlies alpha synuclein turning into lewy bodies |
| mitochondria function | turns O2 to glucose for ATP; energy production! |
| MPP+ vs MPTP | MPTP itself isn’t what damages the cells, but rather the oxidation product MPP+ MPP+ is formed by activity of monoamine oxidase B (MAO-B) in astrocytes & serotonergic neurons and transported by DA transporter into substantia nigra cells and mitochondria |
| how does MPP+ cause cell death through mitochondria | MPP+ builds up and blocks mitochondria respiration (oxygen dependent energy production) mitochondria is unable to replicate DNA; gene replication is the issue since it cant read DNA and make new AND cant make energy, cell dies (buildup= lewy bodies) |
| do pharmacological treatments of parkinson’s cure the disease itself | no, they just treat the symptoms, they dont slow progression of the disease itself |
| treatment for parkinson’s | L-DOPA (can pass B.B.B.and carbidopa (decarboxylase inhibitor, cant pass B.B.B.) MAOIs COMT inhibitors (COMT breaks down DOPA in liver) (more dopa=more DA) |
| why do MAOIs help parkinsons | MAO breaks down catecholamine and seratonin, by inhibiting them this may help the seratonin pathway breakdown symptoms and lack of dopamine issue; gives a greater seratonin and dopamine bioavailability |
| types of atypical antipsychotics | selective D2 (and d3) receptor antagonists DA partial agonists broad spectrum antipsychotics **all treat both + and - Sx |
| broad spectrum antipsychotics | block receptor types in addition to D2 lower seizure threshold heterogenous class (misfit toy class kinda…no 1 things they all have in common |
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