midterm #2 Flashcards
operationalization of stimulants:
biological (3)
behavioural (4)
biological:
- substance raising levels of physiological activity in the body
- objective
- sympathomimetic (cause physiological arousal, suppress parasympathetic nervous system)
behavioural:
- substance temporarily improving mental/physical function
- subjective
- improvement depending on functionality
- James-Lange theory: attribution can change interpretation (panic vs. happy)
state-dependent memory
when memory eretrieval is more accurate under the same conditions as memory encoding
speed/accuracy tradeoff with stimulants
new behaviours: tradeoff
learned behaviours: no tradeoff with stimulant, good performance
adenosine functions (2)
+ A1 receptor (2)
+ A1 and A2 receptors (2)
- inhibitory effect (glutamate antagonist)
- dopamine antagonist
- A1 receptor:
- slowing metabolic function
- postsynaptic depression of NMDA receptor important for learning
- A1 and A2 receptors:
- reducing heart rate
- opening blood-brain barrier
caffeine behavioural effects
mood 2 + performance 4
mood elevation
- placebo (dopaminergic release)
- emotional physiological attribution
performance enhancement
- enhanced in boring/simple tasks
- disruptive or neutral in complex tasks
- impaired decision-making in motor control
- decrease in fatigue (but not getting better)
caffeine absorption and elimination
- time to peak/saturation is same across doses
- more experience -> longer effects (though reverse in cigarette smokers)
caffeine tolerance and withdrawal + issues (3)
only physiological, not psychological
issues:
- variability of absorption in studies
- withdrawal or dehydration
- small rates of systematic reported effects (11%)
energy drinks + issues (3)
combination of xanthines + potentiatiors
issues:
- highly variable xanthine content
- natural caffeine doesn’t need to be listed
- metabolites and precursors not measured
Taurine (4)
- similar to GABA: inhibitory in adults, excitatory in children
- anxiolytic effects
- shuts off acetylcholine retrograde learning mechanism
- neuroprotectant (inhibits glutamate-induced excitotoxicity, antioxidant)
Caffeine and Taurine together
- synergistic effects: caffeine extremely potentiated
- aerobic heart pattern despite feeling chill
cocaine: administration (three ways)
chewing leaves
- alleviates pain
- alleviates altitude sickness
inhaling
- paste mixed with kerosine: toxic
- freebase: extracted paste, explosive
- crack: freebase mixed with baking soda and water
injecting:
- hydrochloride: salt form of freebase
cocaine: neuropharmacology (3)
reuptake inhibitor in mesolimbic pathway,
blocks transporter protein
- reward: VTA
- disordered thought/speech: PFC, nucleus accumbens
issues in cocaine effects (3)
1) where does euphoria come from (dopamine, but not serotonin is affected, so wtf)
2) other transporter protein antagonists don’t induce euphoria
3) sensitization: larger euphoria and crashes in heavy users than non-heavy users
CART (cocaine and amphetamine regulated transcript)
midbrain and hypothalamus
midbrain: neuromodulator produced after psychostimulation
- if released with dopamine, inhibits action -> post-crash depression
hypothalamus: starvation
- responsible for decrease in eating behaviour(anorectic)
cocaine as antagonist
closes sodium channels -> no electric propagation -> anaesthesia
cocaine: long-term effects
- anxiety/depression (downregulation in limbic system)
- tremor (downregulation in midbrain)
- suicide (motivation and disinhibition remain active)
- delay discounting (evaluate outcomes differently based on when they’re obtained, especially for cocaine)
cocaine: tolerance (rapid and physiological)
rapid tolerance:
- coke-out (over 10-24h, same dose not same effect)
- freeze (psychic numbing followed by exhilaration
- let-down (depression after 1st dose due to coke-out)
physiological:
- slow
- heart-rate and blood-pressure effects
amphetamine: mechanisms
- molecular effects (3)
- creates leaky vesicles
- inhibits MAO (increase in dopamine)
- inhibits reuptake of norepinephrine (9x), dopamine
amphetamine:
- Benzedrine
- methylated amphetamine
- ADHD treatment (dex vs levo)
Benzedrine:
- appetite suppressant, decongestant
methylated amphetamine:
- quicker passage across blood-brain barrier
ADHD treatment:
- dex: higher binding affinity
- levo: more potent but worse at binding
amphetamine: tolerance (2)
- tachyphylaxis
- study: positive effects on first meth days, negative effects on last meth day
amphetamine: dependence (2)
psychological (craving)
- anxiety/depression, sleep
crystal meth: physiological dependence, allostatic changes
amphetamine psychosis (3)
1) chronic use:
- - paranoia, formication
2) delusions, hallucinations
- - dopamine release in limbic system
3) tweaking
- - irritability, violent behaviour
ADHD: vigilant concentration
- brain substrate
- what happens in ADHD
- reticular formation, norepinephrine
- in ADHD: less norepinephrine, less perseverance
- in ADHD: lack of sensitivity to rewards
ADHD: cognitive awareness
- brain substrate
- what happens in ADHD
- mesolimbic/mesocortical dopamine pathway hypoactive
- any reward is motivating: ADHD kids respond to any reward but don’t follow through
- inability to ignore stimuli
Ritalin: neuropharmacology (3)
- reuptake inhibitor for dopamine, norepinephrine
- more potent inhibitor than cocaine
- enters brain more slowly tho
- thus, less abuse potential
Ritalin
- is an amphetamine
(Dextro-) Amphetamines (Adderall) (3)
- uniquely right-rotating
- psychostimulants w/o vasoconstriction in body
- psychoactive (decline in popularity)
(Dextro-) Amphetamines (Adderall): neuropharmacology (3)
1) reverse dopamine transporter
2) create leaky dopamine vesicles
3) norepinephrine affected as well
Ritalin, Adderall, Dex effects and abuse (3)
- only moderate effects on cognition and WM
- no effects on cognition or long-term memory
- used as athletic enhancer (increased perseverance)
ADHD medications: underprescription (3)
- especially in ethnic minorities to escape stereotype
- drug holidays
- gateway drug belief (though actually more drug abuse in non-treated ADHD)
cocaine vs ADHD medication (effects (2) and reinforcement (1))
effects
- compared to Ritalin, shorter time to euphoria
- compared to Amphetamine, less aversive acute and long-term effects
reinforcement
- combined reinforced schedule is best to get off cocaine
permissive hypothesis
low serotonin causes low dopamine/norepinephrine
because if low serotonin, dopamine is compensated as precursor for serotonin -> less dopamine
diathesis-stress model and MDD (3)
- onset of MDD is correlated with stressful traumatic events
- changes in schemas precede both onset and remission of depression, in response to stress
- organic stress (e.g. low sunlight) can also induce depression-like symptoms
first-generation antidepressants (2, what they do, problems)
1) MAO inhibitors
- inhibit MAO breaking down monoamines
- problem: MAO is used for breaking down many things
- - cheese reaction: if no MAO, no tyramine breakdown, stroke
2) tricyclics
- inhibit reuptake of serotonin, dopamine, norepinephrine
- problem: heart-rate irregular or elevated
second-generation antidepressants (1)
SSRIs
- inhibit serotonin reuptake
- fewer cardiologic side effects than tricyclics
- designed based on permissive hypothesis
third-generation antidepressants (2)
SNRIs
- inhibit reuptake of serotonin and norepinephrine
antidepressants, motivation, suicide
> take medication
motivation increases first, before mood
higher readiness to commit suicide (Black Box warning)
but: adolesents as likely to commit suicide on as off medication
other drugs as antidepressants (3)
amphetamines:
- short-term euphoria, no long-term help
oxytocin:
- rewards interpersonal behaviour, in experimental phase
heterocyclics:
- increase serotonin and norepinephrine in synapse
- many problems though, only last resort
problems with heterocyclics (4)
- cardiovascular irregularities
- downregulation of norepinephrine receptors (re-emergence of depressive symptoms)
- high toxicity
- other side effects (e.g. insomnia)
antidepressants: discontinuation syndrome
+ reason given
+ withdrawal vs rebound
+ explanation
tendency to willingly stop taking the medication after 4 weeks, resulting in resurgence of symptoms
- ‘brain shivers’ described after cessation
- not withdrawal or tolerance-induced, but rebound
- explanation:
- feeling better, stop taking meds
- takes long to have effect, think it ain’t working
Glucocorticoid or BDNF theory of MDD
stress -> cortisol -> atrophy of hippocampus -> MDD
glucocorticoid:
- released at end of HPA axis, induces cortisol release
- HPA axis hyperactive
- cortisol leads to changes in PFC, amygdala, hippocampus
- treatment: antagonizing glucocorticoid receptors
BDNF:
- facilitates neurogenesis of hippocampus
- too little BDNF in MDD
- treatment: serotonin agonists increasing BDNF production
MDMA: absorption and elimination (solubility, MDA, CYP2D6)
- highly lipid-soluble
- metabolite MDA: psychoactive
- longer high time
- more potent
- CYP2D6 enzyme needed to metabolize MDMA
- SSRIs inhibit CYP2D6 -> dangerous to take MDMA when on SSRIs, toxicity
MDMA: neuropharmacology (5 effects)
1) MAO-A inhibitor
2) competitive reuptake inhibitor (binds to reuptake transporter proteins)
3) leaky vesicles: expunge neurotransmitters out
4) reverse transport: expunge neurotransmitters out
- low doses: serotonin
- high doses: serotonin and dopamine
5) agonist at 5-HT receptors
- facilitates oxytocin release
MDMA: acute effects (physiological + psychological)
physiological: sympathomimetic
- amphetamine-like
- sudden and extreme sympathomimetic response can lead to physiological problems, e.g. loss of consciousness
psychological: empathogenic
- increased empathy
- mild euphoria due to oxytocin
- sudden sympathomimetic resonse can lead to psychological problems, e.g. panic
MDMA: negative effects (sub-acute, post-withdrawal, general)
sub-acute:
- suicide Tuesday (depression/anxiety)
- sleep disturbances
- > both serotonin-related
post-withdrawal:
- substance-induced paranoid psychosis (low-level, false-yet-feasible beliefs of threat
general:
- selective serotonergic neurotoxin
- relapse of pre-existing mental illness (schizophrenia and bipolar)
- lower seizure threshold
MDMA: tolerance
- mostly connection atrophy between serotonin-neurons, but neurons stay intact
- serotonin downregulation and less serotonin release
- weaker effects with more use
MDMA: dependence
- uncertain, not well documented
MDMA: Brown et al. (2010)
> 3 groups: MDMA users, weed users, controls
match on many variables
test verbal working memory
- > MDMA users poorer performance on all tasks
- > long-term deficits in verbal memory
MDMA: Hyseck et al. (2012)
reading emotions from eyes
> within: sober and high
reading emotions from eyes
- > improved recognition of positive emotion
- > decreased recognition of negative emotion
MDMA: Kirkpatrick et al. (2014)
> sober, placebo, MDMA, oxytocin
morphed facial expressions test
MDMA:
- > decreased ability to recognize angry and fearful faces
- > no impact on happy faces
=> MDMA selectively impacts negative social perceptions
