Download Caffeine - Sleep - Centre Londres 94

Caffeine
& Nicotine
Diani Amaranath
& Shareen
Han
Caffeine - Content
Item
Item Size
Caffeine Content(mg)
coffee
150 mL
60-150
coffee, decaf
150 mL
2-5
tea
150 mL
40-80
chocolate milk
150 mL
2-7
Mountain Dew
355 mL
54
Coca Cola
355 mL
46
Diet Coca Cola
355 mL
46
Sprite and 7-UP
355 mL
0
chocolate bar
50 g
3-63
peanut butter cup
51 g
5.6
chocolate chip cookie
30 g
2-5
MIDOL
1 tablet/capsule
32
*ANACIN
1 tablet/capsule
32
Caffeine - Prevalence
• Worldwide, 120,000 tons of caffeine are consumed
each year
• The highest coffee consuming countries are Finland,
Sweden, Denmark, Norway and Belgium.
• The average daily consumption of caffeine among
adults is 200 mg/day in the United States and Canada
and more than 400 mg/day in Sweden and Finland.
• Women metabolize caffeine about 25% faster than
men
• Why drink coffee?! (most popular source)
- Need for a stimulant
- Preference for coffee
- Knowledge for coffee
• Non-coffee drinkers even get plenty of caffeine:
former coffee drinkers get about 107 mg per day and
people who have never had coffee get about 91 mg
per day
Caffeine – ”Comorbidity”
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smokers
=?
=
mood disorders
substance abuse disorders
Caffeine, drug withdrawal and dependence???
Caffeine - Symptoms
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Reduce fine motor movement
Causes insomnia
Headaches, nervousness and dizziness
Pupil dilation
Liver releases sugar into the bloodstream
Blood vessels near the surface of the skin
constricts
• Increases heart rate
• Bathroom breaks!!! (diuretic)
Caffeine - Neuroanatomy
Prefrontal Cortex
http://www2.onu.edu/%7Eksehlhor/lecture.html#mesolimb
Caudate Nucleus
Caffeine –Adenosine
• methylxanthine
• caffeine increases the turnover of many transmitters,
incl. monoamines (NE, 5-HT) and acetylcholines (ACh)
• adenosine-ant. = DA , Adrenaline
• adenosine decreases the firing rate of neurons and
exerts an inhibitory effect on synaptic transmission
and on the release of most neurotransmitters
• acts on the A1 and A2a adenosine receptor subtypes
• A1 (at high doses)
- linked to adenyl cyclase
- high levels in the hippocampus, cerebral and cerebellar cortex and
thalamus
• A2a (at low to moderate doses)
- interaction with D2 receptors
- almost exclusively located in the striatum, nucleus accumbens and
olfactory tuburcle
Caffeine – Monoamines
• DA nucleus accumbens ???
• DA prefrontal cortex
- Mesocortical subsystem
• DA caudate nucleus
- Nigrostriatal subsystem
• expression of early genes in these areas with
administration of caffeine
• administer an adenosine A2a agonist, decrease the
affinity of DA binding to D2 receptors in the striatal
regions
• caffeine leads to the inhibition and blockage of
adenosine A2a receptors, leading to a potentiation of
dopaminergic transmission
• 5-HT later!!!
Caffeine - Studies
Withdrawal
• Headaches, feelings of weariness,
impaired concentration, fatigue, anxiety,
irritability, increased muscle tension
• onset of caffeine withdrawal effects usually occurs 24 h
and peaks around 24-48 h (can appear within 3-6 h)
• Experiment - Headaches B4 and After Surgery
- Before and after surgeries, patients are usually told to fast for “X” amount
of time
- For every 100 mg increase in daily coffee consumption, the risk of
headaches immediately before and after surgery is increased by 12-16%
respectively, and also correlates with the duration of fasting
- Risk of headaches reduce with caffeine substitutes (pills)
- Caffeine withdrawal symptoms disappear soon after the absorption of
caffeine in the blood
- caffeine withdrawal, headaches and cerebral blood flow ???
Tolerance
Caffeine - Studies
• Seen in monkeys, mice, cats and squirrels
• Reinforcement threshold for electrical brain stimulation
• Tolerance development for animals and humans, including the
effects of caffeine on blood pressure and heart rate, plasma
adrenaline and NE levels and renin activity
• Some indications of tolerance of caffeine in sleep: heavy coffee
drinkers vs. non-coffee drinkers
No tolerance development for caffeine???
• Limited evidence for tolerance in caffeine-induced alertness and
wakefulness
• Lack of tolerance of cerebral energy metabolism to caffeine:
subjects had the same metabolic increases when administered of 10
mg/kg caffeine daily for 15 days (controls were injected with
saline)
Tolerance for caffeine remains unclear
• Speculated that if tolerance to caffeine does exist it does not
involve the adaptive changes in adenosine receptors but rather the
DA system as a result of the chronic adenosine receptor blockage
Caffeine - Studies
Reinforcement
• in rats, intravenous self-administration of caffeine via a
lever (some of these studies, only a subset of the
subjects pressed the lever)
• in nonhuman primates, self administration was sporadic:
periods of high frequency followed by periods of low
frequency
• caffeine was able to reinstate an extinguished cocaine
self-administrating behaviour
• dose dependent: 20-25mg = reinforcing properties, 50100mg = decrease, 400-600mg = adverse
- occurs in 100% of heavy coffee drinkers (1020-1530
mg/day)
- occurs in 45% of moderate coffee drinkers (128-595
mg/day)
Caffeine - Studies
Dependence
• 99 subjects (U.S.)
• 16 of which filled the criteria for caffeine dependence
• dependence was not related to the amount of caffeine
consumed daily
• ranged from 129 to 2548 mg/day, median 360 mg
• of the 16 subjects who were diagnosed as having a
“caffeine dependence”…
- 10 had a history of substance abuse disorder
- 7 had a history of a mood disorders
• these results are concurrent with other findings in the
past where caffeine use was more prevalent in those who
also consumed nicotine and alcohol
Caffeine - Sleep
• Areas that control mood and sleepwake functions are highly sensitive
to caffeine
• Regions include:
1. medial raphe (MRAP)
2. dorsal raphe (DRAP)
3. locus coeruleus (LC)
• i.e. 200 lbs, 1 mg/kg = 1 cup of coffee
• 5-HT: increase, promotes sleep
decrease, reduces sleep
• NE: increase, reduces sleep, inhibits REM sleep
lesion LC, abolish muscle tone in REM sleep
Caffeine – Sleep (again)
• benefits of sleep…
- restorative properties = helps the body recover from the
activities during the day
- deprived of stage 4 sleep, people complain about being
physically tired
- adaptive for animals who hibernate, are nocturnal or diurnal
• shortens the time spent in various phases of
slow wave sleep (repairing stages of sleep)
• phases of REM sleep is preserved
• prolongs sleep latency
• caffeine withdrawal-induced behavioural
changes usually last a dew days but the
disruption in sleep-related signs have been
shown to last up to 30 days after the onset of
the withdrawal symptoms
Caffeine – Long Term Aversive
Effects
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Caffeine dependence
Infertility
Birth defects
Weight-loss
Pancreatic Cancer
(Wilcox, 1988)
Caffeine – Benefits???
At low to moderate doses…
• increases ACh synthesis (LTP and memory)
• alertness (memory)
• ability to concentrate
• speeds up reaction time
• Anacin – relieves vascular headaches
Caffeine – Future Studies
Parkinson’s Disease
(Ross et al., 2000)
• PD = decrease in DA BUT, caffeine increases DA
• 8,004 Japanese American men, 102 developed PD
• PD incidence, correlates negatively with the amount
of coffee consumption
• Caffeine from other sources
such as green tea and
chocolate were also
associated with a lower
risk in PD
A little 4-1-1…
+
=
Caffeine does NOT counteract the effects of alcohol!!!
Drug tests include caffeine! Athletes are disqualified if
their concentration exceeds 12 micrograms of caffeine
per mL of urine.
NICOTINE
OVERVIEW
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Epidemiology
Comorbidity
Maternal Consequences
Genetics
Brain reward circuit
Neurotransmitters
Tolerance / Withdrawal
Treatment
Long-term effects / Benefits
Conclusion
EPIDEMIOLOGY
• Lifetime prevalence - 24%
• Highest risk for nicotine dependence
occur in the first 16 yrs after smoking
began
• Gender differences
COMORBIDITY
• Comorbid with depression and
schizophrenia
• Psychiatric comorbidity in adolescents
• Early onset of cigarette smoking and
conduct problems- increased
psychopathology
Maternal Consequences
• In utero nicotine exposure in animal
models:
– growth suppression
– disturbances in neuronal pathfinding,
– abnormalities in cell proliferation and
differentiation
– disruptions in the development of
cholinergic and catecholaminergic
systems.
Maternal Consequences
• Prenatal exposure to nicotine in humans:
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risk of developing ADHD
low birth weight
elevated blood pressure
dysregulation in neurodevelopment
higher risk for psychiatric problems
GENETICS
• Family studies:
– high vulnerability
• Parental alcoholism and nicotine
dependence
– Adult children of alcoholics (ACOA) high risk of developing nicotine
dependence (13.3%)
– ACOA started regular nicotine use
earlier
Brain Reward Circuit
• Nicotine receptors in the CNS found on
presynaptic dopaminergic and
serotonergic neurons in the brain
• Neurons in Substantial Nigra and VTA
are important in cigarette addiction
Reward Pathway
NEUROTRANSMITTERS
Glutamate / GABA
• Nicotine increases glutamate in the
VTA, Nucleus accumbens, prefrontal
cortex
• Glutamate antagonist:
– reduce nicotine self-administration in mice
• GABA agonist:
– reduce nicotine self- administration in rats
Soluble Gases
• Nicotine modulate effects on Nitric
Oxide
• increase Nitric oxide indirectly via
glutamate receptors
• increase in the cortex and hippocampus
Dopamine
• Increase extracellular dopamine
concentration
• inhibit uptake of dopamine through
nicotinic acetylcholine receptors
• increase release of dopamine in the
nucleus accumbens
Dynamics of Addiction
Tolerance (Addiction Cycle)
Tolerance
• Repeated exposure to nicotine =
increase nicotinic acetylcholine
receptors
• Tolerance builds up during the day
• Night Abstinence : regain sensitivity
to nicotine
• Smokers use cigarettes to:
– regulate amount of nicotine
– stay in the neutral zone
– avoid withdrawal symptoms
Withdrawal
Withdrawal Symptoms
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Restlessness
Irritability
Anxiety
Drowsiness
Impatience
Confusion
Impaired concentration
Withdrawal Symptoms
• Physical signs
– decreased heart rate
– decreased urinary excretion of Epinephrine
, Norepinephrine and Cortisol
– gain weight (~ 5 pounds)
• absence of anorexic effects of nicotine
• decrease metabolic rate
– craving persist for months to years
Neurobiology of
Withdrawal symptoms
• Central and peripheral populations of
nicotine acetylcholine receptors:
involved in mediating SOMATIC signs
• Only Central populations of nicotine
acetylcholine receptors: involved in
mediating AFFECTIVE signs
Treatment
• Oral nicotine solution
• Nicotine replacement therapy (NRT)
• Bupropoin SR
– reduces withdrawal symptoms and weight
gain
• Behavioral Counseling
• Antidepressants - Comorbidity
Long-term Effects/
Benefits
• Changes in nicotinic acetylcholine
receptors (nicotine addiction)
• elevation of nerve growth factor
• enhance learning
• protection of neuronal loss
• preventive factor against
neurodegenerative disease (Alzheimer’s
and Parkinson’s disease)
• Cognitive benefits in Schizophrenia
Future Studies
• Effectiveness of nicotine as treatment
for neurodegenerative diseases
• Is nicotine dependence a consequence
or a cause of environmental factors
versus biological factors