Exam 3 Flashcards
serotonin is synthesized from what
tryptophan
two steps to serotonin synthesis
catalyzed by TPH and AADC
TPH2
in serotonergic neurons
how is serotonin synthesis regulated
enzymatic activity and precursor activity
why does tryptophan compete with amino acids
to cross the blood brain barrier and increase serotonin
what diet increases ratio of tryptophan
low protein high carbohydrate
what does elevating tryptophan do
enhance cognitive functions (memory, attention), elevate mood, improve sleep
tryptophan loading
administration of pure tryptophan
if you inhibit TPH you get
less serotonin
reducing serotonin via ATD method does what
impairs memory consolidation of verbal information but has no influence on working memory and attention
serotonin is transported into synaptic vesicles by
VMAT2
reserpine does what
depletes serotonin (broken down when not in vesicles)
terminal autoreceptors do what to serotonin
directly inhibit release
somato-dendritic autoreceptros do what to serotonin
inhibit release by slowing rate of nerve firing
what reuptakes serotonin
SERT
antidepressant drugs
SSRI’s
how do SSRIs work
by blocking the serotonin transporter
where are serotonergic neurons found
along the midline of the brainstem (raphe nuclei)
what are the roles of dorsal raphe nucleus (DRN) and median raphe nucleus (MRN)
give rise to most of the serotonergic fibers in forebrain
when awake, how do serotonin cells fire
a regular rate (tonic firing)
how do serotonin cells fire when in slow wave sleep
irregularly
slow tonic firing of DRN neurons promotes what
non REM sleep
burst firing of DRN neurons promotes what
wakefulness
where is serotonin 1a receptor concentrated
in hippocampus, septal area, and DRN
what does the serotonin 1A receptor do
inhibit adenylyl cyclase to decrease cAMP, increase opening of K+ channels and membrane hyperpolarization
what kind of receptor is serotonin 1A
autoreceptor and postsynaptic
where are serotonin 2A receptors located
cortex
what do serotonin 2a receptors do
increase Ca2+ levels in postsynaptic cell and activate protein kinase C
what kind of receptor is serotonin receptor 2A
activating
most serotonergic neurons in the CNS are located
raphe nuclei
serotonin has a key role in regulation of
anxiety through postsynaptic serotonin 1A receptors
serotonin deficiency hypothesis
low CNS serotonergic activity is associated with hyper aggressiveness
what is a behavior/function influenced by serotonin
anxiety, appetite, and sleep
what does MDMA do
stimulates release of serotonin from nerve terminals and inhibits reuptake
effects of MDMA
heightened arousal, euphoria, enhanced perceptual awareness, prosocial effects
high MDMA doses result in
serotonin depletion (in animals)
designer drugs
synthetic cathinone and amphetamine variants
synthetic cathinones
are substrates for dopamine, norepinphrine, and serotonin transporters, and cause acute release of dopamine, serotonin, and norepinephrine
what kind of drugs are opioids
narcotic analgesics (reduce pain without producing uncosciousness)
psychoactive ingredients in opiates
morphine and codeine
partial agonists
less analgesic effect, reduced risk of dependence
antagonist
can prevent or reverse effects of opioids (treatment for overdose)
which reaches the brain faster: heroin or morphine
heroin
adverse affects of opoids
restlessness, anxiety, nausea/vomiting
higher doses of opiods
abnormal state of elation or euphoria
low to moderate dose of opioid
pain relief, constricted pupils, drowsiness, inability to concentrate, dreamy sleep
respiratory failure is the ultimate cause of death in overdose because
morphine acts on the brainstem’s respiratory center
how can naloxone’s blocking effects be overcome
by increasing concentrations of morphine, showing competition for the receptor
types of opioid receptors
mu, delta, and kappa
mu receptors
have a high affinity for morphine, wide distribution in brain and spinal cord
delta receptors
found in forebrain, modulate olfaction, motor integration, reinforcement, and cognitive function
kappa receptors
found in striatum and amygdala, hypothalamus and pituitary, participate in regulation of pain perception, gut motility, and dysphoria
all opioid receptors are coupled to
G proteins (metabotropic, all inhibitory)
postsynaptic inhibition
opens potassium channels, hyperpolarization
axoaxonic inhibition
closes calcium channels, decreases amount of transmitter released
presynaptic autoreceptors
reduce release of a co-localized transmitter
mu and delta receptor join to form
a heterodimer
opioid ligands are
peptides
mu receptor binds to
endomorphins and endorphins
delta receptor binds to
enkephalin
kappa receptor binds to
dynorphins
first (early) pain
immediate, sensory component, goes from spinal cord to thalamus
second (late) pain
emotional component, goes to anterior cingulate cortex
opioids reduce transmission of pain signals at the spinal cord in two ways
inhibitory spinal interneurons: release endorphins that inhibit activation of spinal projection neurons
descending modulatory pathways: inhibit projection neuron or excitatory interneuron, or excite inhibitory opioid neuron
opioid drugs inhibit
inhibitory GABA cells, increasing mesolimbic cell firing and dopamine release in NAcc
cross tolerance
related drugs also show reduced effectiveness
physical dependence
lack of drug causes withdrawal
cross dependence
administering any other opioid drug will stop or reduce withdrawal
acute effects of opioids are the opposite of
withdrawal symptoms
methadone
reduces symptoms to a comfortable level, reduces euphoric effect of heroin
clonidine
acts on noradrenergic autoreceptors to reduce norepinephrine activity in locus coeruleus
buprenorphine
opioid partial agonist used in the same way as methadone
medication assisted treatment
a combination of detoxification, pharmacological support, and group/individual counseling
glutamate
ionized form of glutamic acid formed from glutamine (an excitatory amino acid neurotransmitter)
vesicular glutamate
transporters move glutamate into synaptic vesicles: VGLUT1, 2, and 3
glutamate uptake
5 different excitatory amino acid transporters (EAATs)
astrocytes
express EAAT2 and may account for about 90% of total glutamate uptake
astrocyte transporters
convert the glutamate uptaken to glutamine using glutamine synthetase
ionotropic glutamate receptors
depolarize the membrane of the postsynaptic cell (excitatory)
AMPA receptor
fast excitatory responses to glutamate
Kainate receptor
selective agonist kainic acid
NMDA receptor
allows both Na and Ca to pass, agonist NMDA
unique characteristics of NMDA receptors
simultaneous binding of glutamate and a co-agonist
binding site for Mg in the ion channel
channel only opens if both co-agonist binding and depolarization of cell membrane occur
metabotropic glutamate receptors
group 1: postsynaptic, activate second messenger system, excitatory
group 2 and 3: presynaptic, reduce transmitter release, inhibit cAMP formation, autoreceptors
long term potentiation
release of glutamate coupled with strong activation of NMDA receptors can lead to strengthening of that synapse
excitotoxicity hypothesis
excessive exposure to glutamate causes prolonged depolarization of receptive neurons, leading to damage or death
GABA
major inhibitory amino acid transporter
GABA is synthesized from
glutamic acid decarboxylase (GAD)
moves GABA into vesicles
VGAT
GABA is metabolized to succinate by
GABA-T
GABA a receptor
ionotropic, causes hyperpolarization and inhibition of postsynaptic cell, consists of 5 subunits
GABA a receptors are sensitive to
CNS depressant drugs
GABA b receptor
metabotropic, postsynaptic, inhibits neuronal firing and adenylyl cyclase
Presynaptic GABA b receptors inhibit
transmitter release and adenylyl cyclase
diverse group of compounds that depress the CNS and behavior
alcohol, barbiturates, non-barbiturate hypnotics, anxiolytics
the calming of mental excitement or abatement of physiological function
sedation
to produce sleep
hypnosis
behavioral effects of alcohol are described through
blood alcohol concentration (BAC)
alcohol is oxidized by
alcohol dehydrogenase and aldehyde dehydrogenase (ALDH)
when alcohol is consumed on a regular basis, these liver enzymes increase in number, increasing the rate of metabolism of alcohol/other drugs
induction
in a single exposure, effects are greater while blood level is rising and smaller while blood level is falling
acute tolerance
increase in P450 liver microsomal enzymes that metabolize alcohol
metabolic tolerance
neurons adapt to continued presence of alcohol by making compensatory changes in cell function
pharmacodynamic tolerance
practicing behaviors while under the influence of alcohol allows adjustment and compensation
behavioral tolerance
intensity and duration of withdrawal is dependent on amount and duration of drug taking
physical dependence
permanent damage to thalamic nuclei and brain regions involved in memory subsequent to vitamin B1 deficiency
korsakoff syndrome
symptoms of fetal alcohol syndrome
intellectual disability, developmental delays, low birthweight, neurological problems, head/facial malformation
why are animal models vital for alcohol research
kept in controlled environment, eliminates poor nutrition, psychiatric disorders, other drug use, genetic engineering can be used
cell membrane lipids become more fluid, changes relationship with membrane proteins
nonspecific action
influences ligand gated channels and alters second messenger systems
specific actions
acute alcohol inhibits
glutamate transmission and glutamate release
acute alcohol increases
GABA effects at GABA a receptor
