Nicotine and caffeine Flashcards
Describe nicotine
- Acts as an agonist at the nicotinic
acetylcholine receptor (NAChR)
Describe routes of administration
- Available by oral (chewing tobacco), inhalation
(cigarettes, cigars, and pipes), intranasal
(insufflation – snuff), transdermal (patch) - Nicotine reaches the brain from the lungs ~ 7
seconds after inhalation - Much faster than intravenous injection
Describe brain areas affected by nicotine administration
- High affinity NAChR found in
ventral tegmental area - Peripheral receptors are found in the
autonomic ganglia (sympathetic and
parasympathetic)
Describe nicotine reinforcement
Cholinergic inputs to the ventral
tegmental area are responsible for
activating mesolimbic dopamine
neurons.
Nicotine activates NAChR on the
mesolimbic dopamine projections from
the VTA to the nucleus accumbens to
moderate nicotine’s reinforcing effects.
Describe nicotine’s effects in current smokers
- Nicotine administration results in
increased calmness and relaxation - Nicotine increases performance on
cognitive tasks - Increases attention
- Enhances mood
Describe nicotine’s effects in non-smokers
- Nicotine administration results in
anxiety, heightened tension, light-
headedness, dizziness, and nausea - Nicotine in high doses decreases
reaction time
Describe reaction time tests
- Nicotine decreases reaction time in a
trial requiring sustained visual attention. - Current smokers had a greater
sensitivity to nicotine than did non-
smokers (lower doses of nicotine effective
at reducing reaction time). - Abstinent smokers had a longer
reaction time than non-smokers –
suggesting the stimulant effects of nicotine
may at best compensate for a deficit.
Describe nicotine tolerance and dependence
- Nicotine is well known to develop acute
and chronic tolerance and dependence - Acute tolerance develops due to
inactivation of NAChR - After first cigarette of the day nicotine
remains high enough in blood to
desensitize NAChR - Levels drop overnight or with several hours
of abstinence
Describe nicotine self-administration studies
- Suggests adolescence is a particularly
vulnerable period for development of
addictions.
Describe what happens when nicotine poisoning is untreated
If untreated:
* Convulsions
* Respiratory failure due to depolarization block of
diaphragm
Describe some reasons why people smoke
- Mood effects:
- Chronic smoking decreases
monoamine oxidase levels in the
brain and periphery - Increased monoamines (DA, 5-HT, NE)
- Antidepressant effects
- Satiety:
- Smoking supresses appetite
- Weight gain common rebound effect of
cessation - Many of the stimulant effects are
proposed to act only to attenuate
withdrawal-associated deficits - Withdrawal includes irritability,
stress, poor concentration
Describe caffeine characteristics
- High absorption from oral doses
- Stimulant and anxiogenic
What is caffeine?
- Caffeine is a xanthine
alkyloid - Structurally analogous
to the neuromodulator
adenosine (nucleoside and neuromodulator)
Describe caffeine’s biphasic effects
- Increased locomotion at low
dose - Decreased locomotion at high
dose - In blinded studies vs placebo
caffeine increased alertness
and decreased tension,
decreased reaction times - In abstinent coffee drinkers
Describe the therapeutic effects of caffeine
- OTC analgesics
- Caffeine has been shown
effective at treatment for non-
migraine headache - Apneic episodes in newborns
- Periodic cessation of breathing,
common in premature infants - Principal treatment is caffeine or
theophylline
Describe caffeine tolerance
- Tolerance develops to some subjective effects of caffeine
- Acute tolerance allows one to fall asleep after a late-night cup of coffee
- Physiological and psychological symptoms of
withdrawal: - Headache, lethargy, fatigue
- Impaired psychomotor performance
- Mild anxiety or depression
- If abstinent withdrawal may last a few days before
dissipating
Describe caffeine dependence
- Caffeine can excite the mesolimbic DA pathway but
only at very high doses - 5-10 X above ‘normal’ doses
- Well demonstrated but considered relatively harmless
- Behavioural / psychological dependence (not
pharmacological) plays a significant role in reinforcing
effects of caffeine - Most chronic coffee drinking is to provide relief of
withdrawal
Describe biochemical effects of caffeine
- Caffeine acts at many sites in the CNS
including GABAA receptors and eliciting
Ca2+
-release within cells, but most likely
exerts stimulant effects by antagonising
adenosine receptors. - Adenosine is elevated in the cat brain
after periods of long wakefulness (sleep
deprivation) and is suggested to signal
increased sleep pressure. - Blockade of adenosine receptors reduces
drowsiness.
Describe adenosine
- Inhibitory at multiple sites in the
hypothalamus - Suprachiasmic nuclei (SCN)
- Lateral hypothalamus (LHA)
- Preoptic areas (MnPO, VLPO)
