Final Exam Flashcards
(122 cards)
1
Q
GABA is synthesized by the enzyme:
A
glutamic acid decarboxylase (GAD) from glutamate
2
Q
GABA is moved into vesicles by:
A
vesicular GABA transporters (VGAT) which also transports glycine (aka vesicular inhibitory amino acid transporters VIAAT)
3
Q
GABA is removed from the synaptic cleft by:
A
GABA transporters: GAT-1, GAT-2, GAT-3 on neurons and glia
4
Q
GABA is broken down in the synapse by:
A
GABA aminotransferase (GABA-T) to produce succinate and glutamate, present on GABAergic neurons and astrocytes
5
Q
in astrocytes, GABA is broken down to glutamate and then:
A
glutamate is converted to glutamine (glutamine synthetase) which is then released and taken back up into the neuron for reuse
6
Q
GABA is only synthesized in:
A
GABAergic neurons
7
Q
where are GABAergic neurons distributed?
A
local interneurons in cortex and hippocampus, sends projection neurons to other regions
8
Q
GABA A receptor
A
ionotropic, allows chloride ion influx, causes hyperpolarization of postsynaptic cell firing, has 5 subunits (most common = 2 alpha, 2 beta, and a gamma or delta)
9
Q
GABA A receptors are sensitive to:
A
CNS-depressant drugs (antianxiety, sedatives, anticonvulsants, benzodiazepines, barbiturates, ethanol)
10
Q
what determines if GABA A receptors are sensitive to benzodiazepines?
A
the gamma subunit
11
Q
what are the effect of benzodiazepines on GABA A receptors
A
potentiating effects, acts on sites distinct from the GABA binding site, increases potency of GABA to open the receptor channel but cannot open the channel without GABA
12
Q
what are the effect of barbiturates on GABA A receptors
A
causes opening of channel even if GABA is not present
13
Q
GABA A agonist
A
muscimol (mushroom), effects include macroscopia (perception of objects as larger than they really are)
14
Q
GABA A competitive antagonist
A
bicuculline (administered systemically, has potent convulsant effects-blocks GABA = too much excitation from excitatory neurotransmitters)
15
Q
GABA A noncompetitive antagonist
A
pentylenetetrazol, picrotoxin (convulsant drugs inhibit GABA A function by acting at distinct sites from GABA binding site)
16
Q
GABA B receptor
A
metabotropic, inhibitory effect on postsynaptic cells by inhibiting cAMP formation and inhibiting potassium channel opening
17
Q
GABA B selective agonist
A
baclofen (muscle relaxant and anti-spastic agent, turns off excitation of muscle contractions)
18
Q
some forms of epilepsy are linked to mutations in:
A
GABA A receptor subunits: some neurons exhibit periodic episodes of prolonged depolarization, followed by hyperpolarization. seizure may be caused by a decrease in the hyperpolarizing phase
19
Q
liver metabolites of methyl alcohol:
A
formic acid and formaldehyde (causes blindness, coma, death)
20
Q
enzymes involved in alcohol metabolism:
A
alcohol dehydrogenase (converts alcohol to acetaldehyde), acetaldehyde dehydrogenase (converts acetaldehyde to acetic acid)
21
Q
fatty liver
A
caused by heavy use of alcohol: triglycerides accumulate in liver cells
22
Q
alcoholic hepatitis
A
caused by heavy use of alcohol: liver cell damage by accumulation of high levels of acetaldehyde
23
Q
alcoholic cirrhosis
A
caused by heavy use of alcohol: death of liver cells stimulates scar formation and blood vessels carrying oxygen are cut off
24
Q
Korsakoff’s disease
A
caused by heavy use of alcohol (thiamine/vitamin B1 deficiency): confusion and disorientation, tremors, poor coordination, ataxia, anterograde amnesia
25
4 mechanisms for alcohol tolerance
1) acute tolerance (single exposure)
2) metabolic tolerance (increase P450 liver enzymes)
3) pharmacodynamic tolerance (compensatory changes in cell function of neurons - decrease GABA receptors)
4) behavioural tolerance
26
nonspecific action of alcohol
- disturbs the relationship of membrane proteins
- interacts with polar heads of phospholipids
- alters lipid composition
27
specific actions of alcohol
- acts at neurotransmitter binding site
- modifies gating mechanism inside channel
- direct interaction with channel protein
- stimulates Gs (linked to adenylyl cyclase)
28
alcohol is a glutamate antagonist at:
NMDA receptors
29
alcohol has the most potent effect on which receptor?
GABA A receptors, opens chloride channel and hyperpolarizes membrane
30
acute administration of alcohol increases endogenous:
opioid production and release (endorphin and enkephalin)
31
chronic administration of alcohol effect on opioids production and release:
reduces production, contributes to feelings of dysphoria that accompanies chronic alcohol use
32
alcohol and glutamate: acute cellular effects
receptor antagonism and reduces release
33
alcohol and glutamate: chronic cellular effects
up-regulation of receptors and rebound increase in release, extreme hyper excitability and massive calcium influx (rebound)
34
alcohol and glutamate: behavioural effects of acute alchol
memory loss
35
alcohol and GABA: acute cellular effects
acutely enhances GABA-induced chloride influx to hyperpolarize
36
alcohol and GABA: chronic cellular effects
neuroadaptive decrease in GABA function without change in receptor number
37
alcohol and GABA: behavioural effects of acute alcohol
sedative effects (anxiety reduction, sedation, incoordination, memory impairment)
38
alcohol and dopamine: acute cellular effects
acute increase in transmission in mesolimbic tract
39
alcohol and dopamine: chronic cellular effects
chronic effects show reduced firing rate, release, metabolism
40
alcohol and dopamine: behavioural effects acute alcohol
reinforcement
41
alcohol and opioids: acute cellular effects
acute increase in endogenous opioid synthesis and release
42
alcohol and opioids: chronic cellular effects
neuroadaptive decrease in endorphin levels
43
alcohol and opioids: behavioural effects of acute alcohol
reinforcement
44
alcohol and opioids: behavioural effects of chronic alcohol
dysphoria
45
alcohol and dopamine: behavioural effects chronic alcohol
negative affect as a sign of withdrawal
46
alcohol and GABA: behavioural effects of chronic alcohol
tolerance and signs of hyperexcitability during withdrawal (seizures, tremors)
47
alcohol and glutamate: behavioural effects of chronic alcohol
rebound hyperexcitability of the abstinence syndrome, brain damage (massive calcium influx = excitotoxicity)
48
Cloninger's Alcoholic Type I
onset after 25, male and female, more likely to be able to stop alcohol abuse
49
Cloninger's Alcoholic Type II
onset before 25, mostly male, less likely to be able to stop alcohol abuse
50
disulfiram (antabuse)
inhibits alcohol metabolism by ALDH, drinking results in flushing, pounding heart, nausea, vomiting
51
naltrexone
opioid receptor antagonist, reduces alcohol consumption and cravings, reduce positive feeling and subjective "high" by blocking effects of alcohol-induced endorphin release
52
what is the most effective combination treatment for alcohol?
medical management + naltrexone, medical management + CBI (combined behavioural intervention)
53
acetylcholine synthesis
choline + acetyl coenzyme A catalyzed by choline acetyltransferase (ChAT) (this is a reversible reaction)
54
rate of acetylcholine synthesis is determined by:
availability of precursors, rate of cell firing
55
acetylcholine is loaded into vesicles by:
vesicular ACh transporters (VAChT)
56
vesamicol
blocks acetylcholine loading by VAChT, reduces ACh release when neuron fires
57
black widow spider venom
massive release of ACh in PNS, causes muscle pain, tremors, nausea, vomiting, salivation, copious sweating
58
botulinum toxin
inhibits ACh release, causes muscular paralysis
59
acetylcholinesterase (AChE)
breaks down acetylcholine to choline and acetic acid, found in presynaptic and postsynaptic cell, non-reversible reaction (choline is re-used to make more ACh)
60
hemicolinium-3 (HC-3)
blocks choline transporters so choline cannot be brought back into cholinergic terminal from synaptic cleft, reduces rate of ACh production
61
type of ACh receptor on muscle in neuro-muscular junction
nicotinic ACh receptor
62
myasthenia gravis
autoimmune disorder, antibodies against muscle cholinergic receptors (nicotinic ACh receptors) are produced, leads to severe muscle weakness and fatigue
63
treatment for myasthenia gravis
neostigmine and pyrostigmine, don't cross BBB, block AChE in the PNS (prevents inactivation of ACh)
64
Sarin and Soman
"nerve gases" = irreversible inhibition of AChE leads to ACh accumulation and overstimulation of cholinergic synapses throughout CNS and PNS, can lead to muscle paralysis and death by asphyxiation
65
pyridostigmine bromide
interacts with AChE to protect it from permanent inactivation by nerve gase
66
cholinergic system:
- striatum interneurons (movement regulation = balance between ACh and DA)
- basal forebrain cholinergic system (BFCS) (innervates cerebral cortex, hippocampus, limbic structures)
67
ACh stimulation of cholinergic receptors in PFC
role in facilitation of sensory cues, signal detection
68
nicotinic ACh receptors
ionotropic (influx of sodium and calcium causes depolarization), 5 subunits, continuous activation desensitizes, then spontaneously resensitize, mostly present on muscle cells
69
muscarinic ACh receptors
metabotropic (M1-M5), opening of potassium channels causes hyperpolarization and reduced cell firing
70
M5 ACh receptor
found in hippocampus, hypothalamus, midbrain DA areas; contribute to excitatory effect on DA neurons mediated by nicotinic receptors, involved in the rewarding and dependence-producing effects of abused drugs
71
cholinergic drugs (agonists)
parasympathomimetic agents (leads to exaggerated parasympathetic response), ex. muscarine, pilocarpine, arecoline
72
cholinergic drugs (antagonists)
- curare: blocks acetylcholine receptor and causes muscular paralysis without analgesia or altered consciousness
- atropine (inhibit parasympathetic effects)
- scopolamine
73
nicotine metabolism
cytochrome P450 2A6 metabolizes nicotine to cotinine
74
nicotine acts on:
nicotinic acetylcholine receptors (nAChRs) which are ionotropic
-high dosese of nicotine causes persistent activation and biphasic effect (stimulation followed by receptor block)
75
methyllycaconitine
nicotinic antagonist (antagonist at alpha 7-containing receptors), blocks influence of nicotine on omission errors
76
AZD0328
partial agonist at alpha7-containing receptors, improves performance on novel object recognition, potential use as cognitive enhancer
77
acute tolerance of nicotine
develops during the course of the day (increased sensitivity in the early morning compared to end of day), desensitization due to temporary inactivation of receptors
78
chronic tolerance of nicotine
compensatory response causing up-regulation of nicotinic receptors in many parts of the brain
79
smoking cessation medications
bupropion (originally developed as antidepressant: Zyban, Wellbutrin, Valbutran), varenicline (partial agonist for nicotinic receptors in VTA: reduces nicotine cravings and produces less activation of dopamine reward system)
80
mechanism of action of caffeine:
- blockade of A1 and A2a receptors adenosine
- block GABA A receptors (stimulate calcium release)
- inhibition of phosphodiesterase
81
adenosine
neurotransmitter-like function, stimulant properties of caffeine depend on antagonists of adenosine receptors (particularly in the striatum)
-interacts with DA in the striatum to modulate locomotor activity
82
acute physiological effects of caffeine
- increased blood pressure and respiration rate
- enhanced water excretion (diuresis)
- stimulation of catecholamine release from adrenal medulla (stress response)
83
amyloid plaques
accumulation of beta-amyloid protein (beta-amyloid is formed by sequential cleavage of amyloid precursor protein APP by beta-secretase and gamma-secretase)
84
neurofibrillary tangles (NFTs)
firous inclusions in neuron cytoplasm, protein tau (associated with microtubules) is the main component
85
what is the greatest risk factor for genetic contributions to Alzheimer's?
decreased Apolipoprotein E (ApoE) - normally component of very low density lipoproteins and functions to remove excess cholesterol from blood and carry it to the liver for degradation
86
genes known to be involved in AD:
- APP on chromosome 21
- presinilin-1 on chromosome 14
- presinilin-2 on chromosome 1 (mutations result in autosomal dominant alzheimer's disease)
- SORL1 (neuronal receptor for ApoE)
87
transgenic mice with APP mutations
animal model of Alzheimer's: demonstrates memory deficits and neuritic plaques
88
senescence-accelerated prone (SAMP8) mouse
animal model of Alzheimer's: early learning and memory deficits, accumulation of amyloid-beta protein, oxidative damage, Tau phosphorylation (NFTs)
89
beagles
animal model of Alzheimer's: aged beagles can develop learning and memory deficits (cortical atrophy, neuron loss, lack of neurogenesis, amyloid plaques, other damage, do not show NFT)
90
rabbits fed high-cholesterol diets
animal model of Alzheimer's: develop amyloid plaques, NFT, cognitive deficits, neuronal loss in frontal cortex, hippocampus, and cerebellum
91
treatments for Alzheimer's
- cholinesterase inhibitors (improve cognition by increasing ACh in synapse)
- NMDA glutamate receptor antagonist, e.g. Memantine (Namenda) - prevents drastic increase in cell firing that leads to excitotoxicity, prevents cell death and thus accumulation of plaques and tangles
92
descending modulatory pathways
beings in midbrain and inhibits spinal cord pain by transmission by directly inhibiting projection neuron or excitatory interneuron or by exciting the inhibitory opioid neuron
93
opioid neural inhibition
1) postsynaptic inhibition (G protein that opens potassium channels to cause hyperpolarization of postsynaptic cell)
2) axoaxonic inhibition (G protein that closes calcium channels and reduces the release of neurotransmitter)
3) presynaptic autoreceptors (activate G proteins that reduce release of colocalized neurotransmitters)
94
opioids mimic inhibitory actions of endogenous opioids at many states of pain transmission:
1) within spinal cord by small inhibitory interneurons
2) descending pathways originating in the PAG (midbrain/brainstem area)
3) at higher brain sites (effects on emotional and hormonal components of pain response)
95
opioids receptors
mu, delta, kappa nociceptin/orphanin FQ (NOP-R): all receptors linked to Gi proteins that inhibit adenylyl cyclase and reduce cAMP
96
mu-opioid receptors
high affinity for morphine
97
analgesic action of morphine
mu-receptors in medial thalamus, PAG, median raphe, spinal cord
98
feeding and positive reinforcement effects of morphine
mu-receptors in nucleus accumbens
99
cardiovascular and respiratory depression, cough control, nausea and vomiting effects of morphine
mu-receptors in brainstem
100
sensorimotor integration effects of morphine
mu-receptors in thalamus, striatum
101
delta-opioid receptors
predominantly found in forebrain structures, possible role in modulating olfaction, motor integration, reinforcement, and cognitive function
-overlap with mu-receptors =modulation of spinal and supraspinal analgesia
102
kappa-opioid receptors
found in striatum, amygdala, hypothalamus, pituitary (may participate in regulation of pain perception, gut motility, and dysphoria)
103
ketocyclazocine
binds to kappa-receptors, opioid analog that produces hallucinations and dysphoria
104
NOP-R
widely distributed in CNS and PNS, role in analgesia, feeding, learning, motor function, neuroendocrine regulation
105
what are the 4 large propetides (precursor peptides) that are processed into smaller active opioids?
- prodynorphin
- pro-opiomelanocortin (POMC)
- proenkephalin
- pronociceptin/orphanin FQ
106
what endogenous ligand binds to mu-opioid receptors?
endomorphins (role in analgesia, reinforcement, feeding, cardiovascular/respiratory depression)
107
what endogenous ligand binds to delta-opioid receptors?
enkephalin (analgesia, reinforcement, cognitive function, olfaction, motor integration)
108
what endogenous ligand binds to kappa-opioid receptors?
dynorphins (neuroendocrine function, water balance, feeding, temperature control)
109
what endogenous ligand binds to NOP-R receptors?
nociceptin/orphanin FQ (spinal analgesia, supraspinal pronociception, feeding, learning)
110
narcotic analgesics
reduce pain without producing unconsciousness
111
morphine is the main active ingredient in:
opium (extract of poppy plant)
112
heroin
made by adding 2 acetyl groups to morphine, makes it more lipid soluble
113
pure antagonists of opiates
naloxone and nalorphine (prevents or reverses the effects of opioids)
114
natural narcotics
- opium
- morphine
- codeine
- thebaine
115
semisynthetic narcotics
- heroine
- hydromorphone
- oxycodone
- etorphine
116
totally synthetic narcotics
- pentazocine
- meperidine
- fentanyl
- methadone
- LAAM
117
endogenous opioids
- enkephalins
- endorphins
- dynorphins
- endomorphins
118
pharmacokinetics of opioids
- only small fraction of morphine crosses BBB
| - opioids easily cross placenta
119
narcotic antagonists
naltrexone, nalmefene
120
CB1 receptors
CNS
121
CB2 receptors
immune system and other tissues (bone, adipose cells, GI tract)
122
endocannabinoid receptors are:
metabotropic (involve G proteins that inhibit cAMP, inhibit voltage-sensitive calcium channels, open potassium channels)
