Lec #5 Drugs for Attention Flashcards
what brain region determines our state of arousal
reticular activating system (RAS) sets the arousal by releasing the neurotransmitters norepinephrine and acetylcholine (the more neurons, the more arousal)
what are the 5 pro-vigilance neurons that help keep us awake and alert?
- histamine
- dopamine
- norepinephrine
- acetylcholine
- serotonin
According to Yerkes and Dodson, what level of arousal is needed to solve difficult problems?
moderate level of arousal
norepinephrine (or noradrenaline)
neurotransmitter that is associated with a high arousal state, which means increased attention and focus, but also increased fear and anxiety
what are the receptors of norepinephrine (NE)?
- adrenergic receptors= G-protein coupled receptors
- increase of neuron activity, despite GPCRs are able to increase or decrease
phosphodiesterase
enzyme responsible for breaking down cAMP and cGMP into their inactive forms
adrenergic receptors
When norepinephrine binds to adrenergic receptors, it causes the production of a signal called cyclic AMP.
- Cyclic AMP is degraded by phosphodiesterase enzyme.
- Caffeine antagonizes the enzyme that degrades the cAMP, amplifying the signal from norepinephrine.
- This is also why caffeine causes similar symptoms to adrenaline (dry mouth, rapid heart rate).
what happens during a crisis when adrenaline is released into the bloodstream and body experiences a fight-or-flight response?
- increased heart rate
- sweating
- pale skin
- increased NE neurons promoting attention and quick response
what receptors do norepinephrine and dopamine activate?
GPCRs (dopamine receptors), firing more neurons
Acetylcholine
neurotransmitter that is associated with learning and memory, and the death of these neurons is thought to contribute to Alzheimer’s dementia.
what are the two receptors activated by acetylcholine? (can have both excitatory and inhibitory effects)
- nicotinic receptors= sodium ion channels
- muscarinic receptors= G-protein coupled receptors (adrenergic receptors)
histamine
- produced as a neurotransmitter in a small number of neurons with a powerful effect
- active when the brain is awake and inactive during sleep
- drugs that block histamine make you sleepy
orexin
neurotransmitter released as a hunger signal, low blood sugar and promote arousal and vigilance needed to obtain food
2 drugs used to increase attention and vigilance through increasing the levels of dopamine and norepinephrine
- amphetamine
- methylphenidate
what are the dopamine transporters making up the recycling mechanism of neurotransmitters stored in synaptic vesicles?
DAT and NET
what are the similarities between amphetamine and methylphenidate?
- both bind to the dopamine transporter (aka DAT) and the norepinephrine transporter (aka NET)
- used to treat attention-deficit/hyperactivity disorders at low-doses
- reduce appetite and cause sleep difficulties due to an increase in dopamine and
what are the 3 drugs that increase vigilance and performance on tasks that require high levels of arousal? (“smart drugs” that can be addictive)
- Amphetamine (Adderall)
- methylphenidate (Ritalin)
- modafinil (Provigil)
methylphenidate (ritalin)
- blocks the DAT and NET by creating an accumulation of dopamine and norepinephrine
- similar structures and effects to cocaine but has a lower off-set
- prescribed at doses that do not elevate dopamine to a level where it is addictive
amphetamine (Adderall)
- DAT and NET reverser
- dopamine and norepinephrine transporter reverser into the synapse instead of clearing it out. Like methylphenidate, it is formulated for slow-release and at low doses to reduce abuse potential.
what drug is used to treaty narcolepsy= disorder where the normal switch between sleep and wakefulness is not maintained
modafinil
- taken during the day to promote wakefulness
- inhibits the DAT and NET
adenosine
- a byproduct of metabolic activity in the brain – when neurons fire they consume ATP (energy) and it is converted to adenosine.
- Adenosine binds to the adenosine receptor to induce sleepiness. Blocking the adenosine receptor prevents the signal from inducing sleep.
what are the 2 components sleep promoted by?
adenosine and satiety signals
what are the 2 components the arousal system is activated by?
hunger signals and sunlight
circadian rhythm
acts as the body’s internal clock, regulating the timing of sleep and wakefulness by responding to external cues, primarily light and darkness. It helps coordinate the release of hormones, such as melatonin and cortisol, that influence alertness and sleepiness.
how is caffeine a psychostimulant?
- antagonist of the adenosine receptor
- prevents adenosine signal that triggers sleep
- indirectly promotes signaling from adrenaline and norepinephrine
what are the adverse of caffeine, non-addictive?
- potential to develop dependence and tolerance
- dry mouth
- agitation
- nausea/ heartburn
what are the 2 actions of caffeine that increase alertness?
- antagonism of adenosine receptor
- inhibitor of phosphodiesterase enzyme
what are the cocaine effects on dopamine recycling?
- inhibits the reuptake of dopamine by binding to the dopamine transporter (DAT) proteins on the presynaptic neurons.
- increase in dopamine levels in the synapse.
What are the adverse effects of psychostimulants cocaine and amphetamine?
- loss of appetite
- insomnia
what are the amphetamine effects on dopamine recycling?
- cause presynaptic neurons to release large amounts of dopamine into the synapse
- occurs through a complex mechanism involving amphetamines’ ability to enter the presynaptic neuron and disrupt the normal regulation of dopamine release.
- inhibit the reuptake of dopamine to some extent, but their primary mechanism is increasing the release of dopamine.
what drugs are used to treat attention deficit orders?
psychostimulants to dopamine/ adrenaline neurotransmitters and cause the neurotransmitter to be reverse-transported into the synapse
