Sleep Wake Mechanisms and Neurophysiology Flashcards
Acetylcholine is produced from where?
Cholinergic neurons in the pedunculopontine tegmental and laterodorsal tegmental nuclei
2 neurotransmitters that are involved in sleep promotion
Gamma-aminobutyric acid (GABA) and galanin (GAL) from the VLPO
Pathways of the arousal system reach the cerebral cortex through what structures?
Thalamus, hypothalamus and basal forebrain
What class are both caffeine and theophylline and how do they work?
Xanthines
Adenosine receptor antagonists
What effect does an acute infection have on REM, N3 and NREM sleep?
Increased NREM
Increased N3
Decreased REM
What causes the inability to move in sleep paralysis?
Inhibition of motor neurons in the spine by glycinergic and GABAergic mechanisms from the sublateraldorsal nucleus (dorsal pons)
Where is NE produced?
Ventrolateral medulla and locus coeruleus (dorsal wall of the rostral pons in the lateral floor of the fourth ventricle)
Where is acetylcholine produced?
Pedunculopontine and laterodorsal tegmental nuclei (PPT/LDT)
Where is serotonin produced?
Dorsal raphe necleus (DR) located in the dorsal midbrain
Where is dopamine produced (when involved in wakefulness)?
Ventral periaqueductal gray matter (vPAG) located in the midbrain
Where is histamine produced?
Tuberomammillary nucleus (TMN)
(posterior hypothalamus)
Where is orexin (hypocretin) produced?
Lateral and posterior hypothalamus
Where is the VLPO located?
Anterior hypothalamus
What neurotransmitters do the VLPO cells produce?
Inhibitory GABA and GAL
How does the sleep switch work?
VLPO blocks input to the ARAS. The ARAS inhibits the VLPO
What are the 6 cytokines that promote sleep?
- Interleukin 1ß
- IL-6
- TNF alpha
- Nerve growth factor
- BDNF
- GHRF
How does GABA promote sleep?
It inhibits neurons containing:
- NE
- Histamine
- Serotonin
- Hypocretin
- Glutamate
What are the effects of alcohol on sleep?
- Disrupts sleep
- Shortens LTSO
- Decreases REM
- Increases snoring and apnea
Antidepressants that increase REM sleep
Buproprion
Nefazodone
Trazodone
Antidepressants that don’t worsen RLS
Buprioprion
Trazodone
Most powerful REM suppressing antidepressant class
MAOIs (selegiline, tranylcylpromine)
What antidepressant can increase eye movements in sleep?
Prozac (fluoxetine)
- Increased eye movements in NREM
- Can be slow rolling or REMs
- “Prozac eyes”
- Any SSRI can do this
- Thought to be a mild form of serotonin syndrome
What effect do most antidepressants have on REM sleep?
Decrease REM sleep
Prolong REM latency
What are the general effects of antipsychotics on sleep?
Increased sedation
Improve sleep continuity
May slightly increase REM sleep
Sleep effects of corticosteroids
Slight REM suppression
Can disrupt sleep and cause bizarre dreams
Sleep effects of Mirtazepine
Increased sleep continuity and SWS
Can decrease OSA by improving upper airway tone but this is offset by weight gain
Sleep effects of opiates
Sedation
Can disrupt sleep and reduce REM
Central apneas
Sleep effects of benzodiazepines
Suppress N3 and REM
Increase N2 sleep and spindle density
non benzodiazepine receptor agonists (zolpidem) have little effect on sleep architecture (except at high doses)
Sleep effect of amphetamines and cocaine
Suppress REM sleep
Sleep effects of THC
Increases TST and N3
Mild suppression of REM
What effect do SSRIs have on N3 sleep?
Either decrease or no effect on N3 sleep
What effect do TCAs have on N3 sleep?
- amitryptiline
- nortriptyline
- doxepin
They increase N3 sleep
What effect does nefazodone have on N3 sleep?
It decreases N3 sleep
What effect does lithium have on N3 sleep?
It increases N3 sleep
What effect does carbamazepine have on N3 sleep?
It increases N3 sleep
What effect do barbiturates have on REM and N3 sleep?
They decrease both
What effects does lithium have on sleep?
- Increased TST
- Decreased N1
- Increased N2 and N3
- Increased REM latency
- Inconsistent effect on REM
What does nefazodone do to REM sleep?
It increases REM sleep
What is the effect of estrogen on sleep?
- Decreased sleep latency
- Increased TST
- Shortened REM latency
- Increased REM sleep
What are the effect of progesterone on sleep?
- Increased REM latency
- Decreased REM sleep
What happens to acetylcholine, NE and serotonin during REM sleep?
- Acetylcholine increases
- NE and serotonin decrease
- (opposite happens in NREM sleep)
What effect does prostaglandin D2 have on sleep_
Strongly sleep promoting. An increase during sleep deprivation is necessary for NREM rebound
Cholinergic activity is at its highest during what 2 states?
Wake and REM sleep
Sodium oxybate acts on what receptor?
GABA-B
Benzos, barbiturates, alcohol and non benzo-receptor agonists act on what receptor?
GABA A
What are the medications (classes) that suppress REM sleep (7)?
- TCAs (amitriptyline, etc)
- One exception is trimipramine
- MAOIs (phenelzine, selegiline)
- Lithium
- Scopalamine
- Serotonergic drugs
- Sympatholytic drugs (clonidine, phentolamine, beta blockers)
- Stimulants like methylphenidate
What effect does pregabalin have on SWS and REM sleep?
It increases SWS but decreases REM sleep
What receptor does gabapentin and pregabalin bind to?
The alpha 2 delta subunit of the VGCC
What SSRI can decrease both SWS and REM?
Fluoxetine
RBD is how many times more likely to develop in patients taking antidepressants and patients with psychiatric disorders?
- Anti-depressants = 5x more likely
- psychiatric disorder = 10x more likely
