Nicotine Flashcards
Nicotine Acts as an
agonist at the nicotinic
acetylcholine receptor (NAChR)
Nicotine Acute toxicity marked by
nausea,
vomiting, faintness, profuse
sweating, hypothermia, decrease
blood pressure, unconsciousness
Administration
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
nicotine is metabolized
Metabolized in the liver to various metabolites
nicotine Rate of liver metabolism proportional to the
addictive potential in humans
Faster metabolism →
more addictive
High affinity NAChR found in (8)
cortex,
thalamus,
striatum,
hippocampus,
substantia nigra,
ventral tegmental area,
locus coeruleus,
raphe nuclei
Peripheral receptors are found in the
autonomic ganglia (sympathetic and
parasympathetic)
Reinforcement of nicotine
Cholinergic inputs to the VTA 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.
Nicotine is a psychostimulant…
sometimes
Nicotine is a psychostimulant… sometimes (current smokers)
increased calmness and relaxation
increases performance on cognitive tasks
Increases attention
Enhances mood
Nicotine is a psychostimulant… sometimes (non-smokers)
anxiety,
heightened tension,
lightheadedness,
dizziness
nausea
Nicotine in high doses decreases reaction time
Nicotine decreases
reaction time in a
trial requiring sustained visual attention.
Reaction time tests Current smokers had a
greater
sensitivity to nicotine than did nonsmokers s (lower doses of nicotine effective
at reducing reaction time)
Reaction time tests Abstinent smokers had a
longer
reaction time than non-smokers
reaction time findings
the stimulant effects of nicotine
may at best compensate for a deficit.
Tolerance and Dependence nicotine
Nicotine is well known to develop acute
and chronic tolerance and dependence
Acute tolerance of nicotine develops due to
inactivation of NAChR
After first cigarette of the day nicotine
remains high enough in blood to
desensitize NAChR
nicotine levels drop
overnight or with several hours
of abstinence
Chronic tolerance of nicotine
- Animals given a single high dose of nicotine
show decreased locomotion - With daily injections locomotor supression
subsides and is replaced by locomotor
activation
In humans green-tobacco illness is a
reaction common in
workers harvesting
tobacco
Self-administration
In animal models, exposure during
adolescence increases self-administration
of nicotine later in life
In animal models, exposure during
adolescence increases self-administration
of nicotine later in life - suggests
adolescence is a particularly
vulnerable period for development of
addictions.
Addictions treatment - Replacement therapies
Nicotine patches, gum, vapes
Addictions treatment - Antidepressants
Bupropion – non-competitive NAChR
antagonist & DA reuptake inhibitor
Varenicline (Champix) – partial agonist
at the
NAChR
Varenicline (Champix) – partial agonist
at the NAChR - induces
mesolimbic DA, reduces craving
Partial agonism can reduce the
response to
nicotine
AUTONOMIC EFFECTS
Nicotine acts in the autonomic nervous system
Nicotine acts in the autonomic nervous system
Increased heart rate
Elevated blood pressure
Physiological arousal may contribute to
reinforcement
Physiological arousal may contribute to reinforcement
Increases risk of cardiovascular disease and stroke
Parasympathetic activation and nicotine
increased acid secretion in stomach → ulcer
Increased peristalsis in bowel → chronic diarrhea
NICOTINE POISONING early symptoms (8)
Nausea/vomiting
salivation,
abdominal pain/diarrhea
cold sweat,
headache,
confusion,
dizziness,
weakness
NICOTINE POISONING early symptoms followed by
Drop in BP, fainting, breathing difficulty
if nicotine poisoning is left untreated
Convulsions
Respiratory failure due to depolarization block of diaphragm
Why do people smoke?
Mood effects
Satiety
Mood effects of smoking
Chronic smoking decreases
monoamine oxidase levels in the
brain and periphery
Chronic smoking decreases
monoamine oxidase levels in the
brain and periphery - Increased monoamines
(DA, 5-HT, NE
Chronic smoking decreases
monoamine oxidase levels in the
brain and periphery
Antidepressant effects
Satiety and smoking
suppresses appetite - Weight gain common rebound effect of
cessation
Many of the stimulant effects are
proposed to act only to attenuate
withdrawal-associated deficits
Withdrawal of nicotine includes
irritability,
stress, poor concentration