Topic 22: Nicotine and Caffeine

Question 1

What is nicotine?

Answer 1

insecticidal plant alkaloid from the leaves of Nicotiana tabacum

acts as agonist at the nicotinic acetylcholine receptor (NAChR)

acute toxicity marked by nausea, vomiting, faintness, profuse sweating, hypothermia, decrease blood pressure, unconsciousness

Question 2

What is the administration of nicotine?

Answer 2

available by oral (chewing tobacco), inhalation (cigarettes, cigars, and pipes), intranasal (insufflation), transdermal (patch)

nicotine reaches the brain from the lungs ~7 seconds after inhalation: much faster than intravenous injection

metabolized in the liver to various metabolites: rate of liver metabolism proportional to the addictive potential in humans

high affinity NAChR found in cortex, thalamus, striatum, hippocampus, substantia nigra, ventral tegmental area, locus coeruleus, and raphe nuclei

peripheral receptors are found in the autonomic ganglia (sympathetic and parasympathetic)

Question 3

What is the reinforcement pathway of nicotine?

Answer 3

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 nicotines reinforcing effects

Question 4

What are the effects of nicotine in current smokers?

Answer 4

nicotine administration results in increased calmness and relaxation

nicotine increases performance on cognitive tasks

increases attention

enhances mood

Question 5

What are the effects of nicotine in non-smokers?

Answer 5

nicotine administration results in anxiety, heightened tension, light-headedness, dizziness, and nausea

nicotine in high doses decreases reaction time

Question 6

How does nicotine affect reaction time?

Answer 6

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

Question 7

What is the tolerance and dependence on nicotine?

Answer 7

nicotine is well known to develop acute and chronic tolerance and dependence

acute tolerance develops dye 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

chronic tolerance: animals given a single high dose of nicotine show decreased locomotion, with daily injections locomotor suppression subsides and is replaced by locomotor activation

in humans green-tobacco illness is a reaction common in workers harvesting tobacco: more common in non-smokers than smokers

Question 8

What is the self-administration of nicotine in animals?

Answer 8

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

Question 9

What is the treatment for nicotine addictions?

Answer 9

replacement therapies: nicotine patches, gum, vapes

antidepressants: Bupropion, non-competitive NAChR antagonist and DA reuptake inhibitor

varenicline (Champix) partial agonist at the NAChR: increases mesolimbic DA, reduces craving, partial agonism can reduce the response to nicotine

Question 10

What are the autonomic effects of nicotine?

Answer 10

nicotine acts in the autonomic nervous system: increased heart rate, elevated blood pressure

physiological arousal may contribute to reinforcement: increases risk of cardiovascular disease and stroke

parasympathetic activation: increased acid secretion in stomach (ulcer), increased peristalsis in bowel (chronic diarrhea)

Question 11

What is nicotine poisoning?

Answer 11

early symptoms: nausea, salivation, abdominal pain, vomiting, diarrhea, cold sweat, headache, confusion, dizziness, weakness

followed by: drop in blood pressure, fainting, breathing difficulty

if untreated: convulsions, respiratory failure due to depolarization block of diaphragm

Question 12

What are the mood effects of nicotine?

Answer 12

chronic smoking decreases monoamine oxidase levels in the brain and periphery

increased monoamines (DA, 5-HT, NE)

antidepressant effects

Question 13

What are the satiety effects of nicotine?

Answer 13

smoking suppresses appetite

weight gain common rebound effects of cessation

Question 14

What are the stimulant effects of nicotine?

Answer 14

many of the stimulant effects are proposed to act only to attenuate withdrawal-associate deficits

withdrawal includes irritability, stress, poor concentration

Question 15

What is caffeine?

Answer 15

commonly found in coffee beans and tea leaves

consumed by 80-90% of North Americans

high absorption from oral doses

half life of ~4 hours

stimulant and anxiogenic

caffeine is a xanthine aklyloid

structurally analogous to the neuromodulator adenosine

related xanthines are found in many plants (teas, cocoa)

Question 16

What are the behavioral effects of caffeine?

Answer 16

in animals caffeine has a biphasic effect: 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

Question 17

What are the therapeutic uses of caffeine?

Answer 17

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

Question 18

What is caffeine tolerance?

Answer 18

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

Question 19

What is caffeine dependence?

Answer 19

caffeine can excite the mesolimbic DA pathway but only at very high doses

well demonstrated but considered relatively harmless

behavioral/psychological dependence (not pharmacological) plays a significant role in reinforcing effects of caffeine

most chronic coffee drinking is to provide relief of withdrawal

Question 20

What are the effects of caffeine withdrawal?

Answer 20

withdrawal from caffeine induces transient subjective effects

in a blinded trial subjects were maintained on 100 mg daily caffeine, substituted for placebo for 10 days before reinstating caffeine

Question 21

What are the biochemical effects of caffeine?

Answer 21

caffeine acts at many sites in the CNS including GABAA receptors and eliciting Ca2+-release within cells, but most likely exerts stimulant effects by antagonizing 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 induces drowsiness

Question 22

What is adenosine?

Answer 22

among other roles, adenosine provides inhibitory input to ascending arousal systems

inhibitory at multiple sites in the hypothalamus: suprachiasmic nuclei, lateral hypothalamus, preoptic areas

adenosine release inhibits arousal and increases sleep pressure