Exam 4 Flashcards
corticotropin releasing factor (CRF) neurons originating in the amygdala central nucleus do what
project to the locus coeruleus and activate the adrenergic component of the stress response
anxiolytics
drugs to relieve anxiety, these are sedative hypnotics or CNS depressants
primary mechanism of action of anxiolytics
enhancing GABA transmission
longer acting BDZs are
useful hypnotics, muscle relaxants, and anticonvulsants
Buspirone
partial agonist at serotonin 1A receptor, does not enhance GABA action
what is the therapeutic index and abuse potential of SSRIs
high therapeutic index, low abuse potential
patients with anxiety disorders have abnormal
ANS response, higher NE released
why is the amygdala important to emotion processing circuits
receives processed sensory and cognitive information, negative emotional stimuli activate the amygdala in humans
anxiety disorders may be due to an imbalance between
emotion generating centers and higher cortical control
locus coeruleus NE cells are excited by
synaptic input from the CRF neurons in the amygdala
locus coeruleus NE cells are inhibited by
GABA, serotonin, and stimulation of a2 adrenergic somatodendritic autoreceptors
benzodiazepines enhance
inhibitory function of GABA
inhibitory GABA has a major role in modulating anxiety by
glutamatergic neurons from the PFC stimulate GABA neurons in the amygdala
BDZ and barbiturates bind to what to enhance function
GABA a receptors
what other modulators also enhance GABA function
alcohol, naturally occurring neurosteroids
neurosteroid levels tend to be lower in individuals with
general anxiety disorder and social phobia
baseline levels of neurosteroids are elevated in panic disorder but drop when a panic attack is induced, indicating
reduced GABA control of the anxiety
BDZs and barbituartes have binding sites on
GABA a receptors
what are barbituarates used for
anesthesia, seizure control, sleep induction, sedatives, alcohol withdrawl
side effects of barbituarates
induces sleep, reduced REM sleep, mental clouding, loss of judgement, slowed reflexes
what can high doses of barbiturates cause
intoxication, coma/death from respiration, dangerous with alcohol
problems with barbiturates
rapid tolerance, severe withdrawal, low safety margin
desirable effects of barbiturates
anxiety relief, loss of inhibitions, can take the edge off of other drugs
BDZs are highly effective for
anxiety reduction, don’t have side effects of barbiturates
BDZ choice is based on
speed of onset and duration of drug action
acetylcholine is synthesized from
choline and acetyl coenzyme A, catalyzed by choline acetyltransferase (chAT)
ACh is loaded into synaptic vesicles by
VAChT
VAChT can be blocked by
vesamicol
acetylcholinesterase (AChE) breaks down to
choline and acetic acid
drugs that block AChE prevent
inactivation of ACh (this is useful for disorders in which cholinergic transmission is deficient)
interneurons in the striatum
regulate dopaminergic output in the striatum
low dopamine levels cause transmitter imbalance and
hyperactivity of cholinergic neurons (Parkinson’s)
basal forebrain cholinergic system (BFCS)
neurons in several brain areas, origin of cholinergic innervation
different components of the BFCS have different roles in
cognition
cholinergic projections from the medial septum and diagonal band to the hippocampus and are involved in
declarative memories
projections from the nucleus basalis/substantia innominata to the prefrontal cortex are important for
maintaining sustained attention
bursts of ACh release from BFCS neurons play a key role in
detecting and responding to learned sensory cues (in mice)
cholinergic neurons in the LDTg and PPTg stimulate
dopamine neurons and effect drug reward and reinforcement, as well as initiation of REM sleep
two acetylcholine receptor subtypes
nicotinic and muscarinic
nicotinic acetylcholine receptors are
ionotropic, hyperpolarizing, mediate fast excitatory responses in CNS and PNS
how to get an ACh receptor channel to open
all binding sites must be occupied by ACh or another agonist (such as nicotine)
subunit composition determines
key features of a receptor such as affinity of binding sites, ionic selectivity, allosteric binding sites, channel opening/closing kinetics
ionotropic receptors can be
open, closed, or desensitized (channel is closed and won’t open even with bound agonist; can re-sensitize spontaneously)
depolarization block
resting potential of the membrane is lost and cell cannot be excited until agonist is removed and membrane repolarized
muscarinic receptors are
metabotropic, operate via second messengers
M1, M3, M5 muscarinic receptors are
excitatory
M2 and M4 muscarinic receptors are
inhibitory
muscarinic receptors play an important role in
cognitive effects of Ach, motor function, and drug reinforcement
principal metabolite of nicotine
cotinine, catalyzed by cytochrome P450 2A6
nicotine activates
nicotinic cholinergic receptors (nAChRs), ionotropic and produce rapid excitatory responses
the mesolimbic dopamine pathway from the VTA to the NAcc plays a key role in
reinforcement
aversive effects of nicotine
nausea, dizziness, sweating, headache, palpitations, stomachache, clammy hands
a mutation in the a5 gene results in
less aversion to nicotine and heavier smoking
desensitization of central nAChRs results in
acute tolerance
up regulation of nAChR levels results in
chronic tolerance
nicotine resource model
mood control and enhanced concentration are dual motivation
deprivation reversal model
alleviation of irritability, stress, and poor concentration in withdrawal
smoking during pregnancy can cause
stillbirth, SIDS, low birth weight
treatment options for nicotine addiction
self help materials
cessation advice
individual/group counseling
medications
nicotine replacement therapy
relieves withdrawal symptoms with nicotine gum/lozenges, transdermal patch, nasal spray/inhalers
bupropion
a dopamine and norepinephrine reuptake inhibitor and weak nicotine receptor antagonist
varenicline
a partial agonist at high affinity nicotine receptors
cannabis plants contain over 120 compounds called
phytocannabinoids
psychoactive compound in cannabis
THC
mix of dried leaves and flowering tops
marijuana
dried resin consisting of fine outgrowths from top of plant
hashish
organic extraction from hashish
hash oil
most common form of cannabis use, typically in cigarettes
smoking
inhalation of cannabis vapor
vaping
dissolved cannabis oils in food
edibles
what does medical marijuana treat
glaucoma, antiemetic, anticonvulsant, analgesic, appetite enhancer
smoked THC is easily absorbed by
the lungs
oral consumption of THC leads to
prolonged but poor absorption, first pass metabolism
cannabinoid effects are primarily mediated by
cannabinoid receptors
slide 15
psychoactive substance that causes perceptual changes, visual hallucinations, altered awareness of the mind and body, and cognitive distortions
psychedelic drug
in peyote cactus, top is cut off and dried, chewed raw or cooked
mescaline
alkaloid from several mushroom species, dried and eaten raw or made into tea
psilocybin
found in plants indigenous to south america, smoked or snorted, produce a brief high
DMT and bufotenine
synthetic and based on fungal alkaloids
LSD
drug induced psycholysis
psycholytic therapy
patient was given high dose of LSD in hopes of gaining insight into problems
psychedelic therapy
appeared in 2010, synthetic compound
NBOMes
trip state of intoxication phases
onset, plateau, peak, comedown
crossing over of sensations
synesthesia
five dimensions of altered states of consciousness
oceanic boundlessness, ego-disintegration anxiety, visionary restructuralization, reduced vigilance, auditory alterations
serotonin like drugs
LSD, psilocybin, psilocin, DMT, synthetic tryptamines
catecholamine like drugs
mescaline and NBOMes
PCP and ketamine are
dissociative anesthetics
non competitive antagonists at the ionotropic NMDA receptor (bind to a site within receptor’s channel blocking ion flow)
PCP and ketamine
remains trapped in the channel even after the agonist (glut) dissociates from binding site and channel closes
drug molecule
the NMDA receptor blockade on cortical GABAergic interneurons increases
cortical glutamate release
what drugs activate the midbrain dopamine cell firing and stimulate dopamine release in the dorsal striatum, NAcc, PFC
PCP and ketamine
increases in drug liking and desire for more drug is
dose dependent
other non competitive NMDA receptor antagonist
dextromethorphan (OTC cold medication)
biopsychosocial model of addiction
includes full range of pharmacological, biological, and psychological factors that influence addiction risk
incentive sensitization theory of addiction
distinction between liking vs wanting a reward
negative emotional state evoked by drug withdrawal
hyperkatifeia
