Topic 22: Nicotine and Caffeine Flashcards
What is nicotine?
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
What is the administration of nicotine?
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)
What is the reinforcement pathway of nicotine?
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
What are the effects of nicotine in current smokers?
nicotine administration results in increased calmness and relaxation
nicotine increases performance on cognitive tasks
increases attention
enhances mood
What are the effects of nicotine in non-smokers?
nicotine administration results in anxiety, heightened tension, light-headedness, dizziness, and nausea
nicotine in high doses decreases reaction time
How does nicotine affect reaction time?
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
What is the tolerance and dependence on nicotine?
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
What is the self-administration of nicotine in animals?
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
What is the treatment for nicotine addictions?
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
What are the autonomic effects of nicotine?
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)
What is nicotine poisoning?
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
What are the mood effects of nicotine?
chronic smoking decreases monoamine oxidase levels in the brain and periphery
increased monoamines (DA, 5-HT, NE)
antidepressant effects
What are the satiety effects of nicotine?
smoking suppresses appetite
weight gain common rebound effects of cessation
What are the stimulant effects of nicotine?
many of the stimulant effects are proposed to act only to attenuate withdrawal-associate deficits
withdrawal includes irritability, stress, poor concentration
What is caffeine?
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)
What are the behavioral effects of caffeine?
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
What are the therapeutic uses 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
What is 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
What is caffeine dependence?
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
What are the effects of caffeine withdrawal?
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
What are the 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 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
What is adenosine?
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
