Unit 5: Stimulants

Question 1

What is attention?

Answer 1

Attention: selection of information for focused conscious processing
- required for most forms of cognition (ie: working memory, STM, visual memory, auditory memory)
- requires a certain level of vigilance/wakefulness—determined by the neurons in the reticular activating system
- important areas include the cortex (frontal cortex), basal ganglia and thalamus
- impaired attention = defining feature of ADHD (with or without hyperactivity)

Question 2

Reticular Activating System

Answer 2

The Reticular Activating System (RAS) is part of the reticular formation (pons, medulla) and is responsible for setting arousal/wakefulness by releasing neurotransmitters:
- NE: norepinephrine
- ACh: acetylcholine

Question 3

Dopamine & Norepinephrine: on attention/arousal

Answer 3

Low arousal: low levels of DA and NE
- sleepy, drowsy
- low cognitive performance on simple and difficult tasks
- baseline arousal for people with ADHD (wuzup)

High arousal: high levels of DA and NE
- paranoid
- panicky
- low cognitive performance on difficult tasks
- simple tasks benefit from a higher level of arousal

There is a happy medium that is ideal for cognitive functioning and the completion of difficult (high cognitive load) tasks

Question 4

Circadian Cycles: Sleep/Wake Systems

Answer 4

1) Awake/arousal system
- activated by hunger, sunlight
- active neurons/neurotransmitters firing:
- acetylcholine : wakefulness, attention, parasympathetic nervous system functioning (rest & digest)
- histamine : regulating wakefulness, cognitive function
- dopamine : movement, memory, pleasurable reward/motivation
- serotonin : mood, digestion, sleep/arousal
- norepinephrine : attention, focus, fear, anxiety
- orexin : hunger signal, arousal

• increasing the firing of these neurons/increasing synaptic levels of neurotransmitters will promote wakefulness

2) Sleep system
- activated by satiety, adenosine
- during the day, the brain uses energy in the form of ATP; the byproduct of this energy is adenosine (accumulates when awake, cleared during sleep)

Question 5

Psychostimulants

Answer 5

Psychostimulants are drugs that promote wakefulness and attention, and increase motor activity (acting on DA system)

Stimulants:
- caffeine
- cocaine; methylphenidate (similar MOAs)
- amphetamine; methamphetamine (similar MOAs)

Psychostimulants are DAT and NET antagonists (blockers)—work to either:
- (a) block transporter to prevent clearance; causing an accumulation of DA and NE in the synapse
- (b) DAT/NET reverser; causes transporter to push DA and NE back into the synapse

Question 6

Caffeine:
Target, MOA, Drug Class

Answer 6

Target: adenosine receptors
Mechanism of Action: antagonist of adenosine receptors; prevents adenosine signal that triggers sleep
- indirectly promotes signaling from adrenaline and norepi

Drug Class: psychostimulant

Question 7

Caffeine Effects

Answer 7

Caffeine effects:
- alertness
- dry mouth
- agitation
- nausea/heartburn
- diarrhea
- insomnia
- racing heart/arrythmia
- dependence
- tolerance

Fatal overdoses = rare, but possible (cardiac arrest)

Question 8

Caffeine: Two Actions of Arousal

Answer 8

1) Antagonist of adenosine receptor
- adenosine = byproduct of ATP metabolism; binds to adenosine receptor to induce sleepiness
- caffeine antagonizes this receptor, preventing adenosine signaling, maintaining awakeness

2) Inhibitor of phosphodiesterase enzyme
- when norepinephrine binds to adrenergic receptors, it stimulates the production of cyclic AMP
- cAMP is degraded by phosphodiesterase enzyme
- caffeine antagonizes this enzyme, blocking it from metabolizing cAMP, amplifying the alertness signal
- this is why caffeine causes similar symptoms to adrenaline (eg: dry mouth, rapid heart rate)

Question 9

Transporter Antagonists

Answer 9

Two types of transporter antagonists:
1) DAT/NET Blockers (eg: cocaine, methylphenidate)
- inhibits DAT/NET (blocks transporters), allowing dopamine and norepi to accumulate (increases levels of DA and NE) in the synapse and bind to postsynaptic neurons

2) DAT/NET Reversers (eg: amphetamine, methamphetamine)
- inhibits DA/NE reuptake at DAT and NET; instead, reverses the movement of these neurotransmitters—reverse transports DA and NE back into the synapse for re-release
- MDMA (stimulant hallucinogen) = similar reversing process, but with SERT

Question 10

Narcolepsy

Answer 10

Narcolepsy: a sleep disorder where disruptions in sleep architecture prevent quality sleep, resulting in extreme sleepiness during the day
- also causes muscle paralysis (like that of REM sleep)

Question 11

Modafinil

Answer 11

Modafinil increases arousal/alertness by increasing levels of norepinephrine, dopamine and histamine
- inhibits DAT and NET but not very well
- mechanism of action = unknown