Note: Nicotine is addicting, but not associated with psychotic behaviors
Principal metabolite of nicotine
Cotinine
Nicotine acts on which receptor?
nAChR (alpha-4/beta-2)
Nicotine reinforcing behaviors
Increased DA in the nucleus accumbens with a single dose
Reinforces release of dopamine
Activates mesocortical reward system
Acute vs. Chronic tolerance of nicotine and the morning fix
Acute tolerance: within a day; as the day goes on, you don't get the same level of satisfaction from a cigarette; however overnight start undergoing withdrawal and the first cigarette in the morning is often the most pleasurable (morning fix)
Chronic tolerance: what it sounds like
Pharmacokinetics of nicotine: distribution half-life and elimination half-life
Rapid to brain (7 seconds)
Distribution half-life: 9 mins
Elimination half-life: 2 hours (reason for morning fix - after 8 hrs of sleep already passed 4 half lives)
Half-life of cotinine
19 hours
Cigarettes (induce/inhibit) some P450 enzyme systems.
Induce
Insula and quitting smoking
Damage to insula = easier to quit
Possible connection between insula and maintaining addiction
Pharmacological treatments of nicotine addiction
Nicotine replacement
Bupropion
Varenicline (Chantex)
Nicotine replacement therapies
Nicotine gum
Nicotine lozenge
Transdermal nicotine patch
Nicotine nasal spray (prescription)
Nicotine inhaler (prescription)
Varenicline
Alpha4/beta2 partial agonist
Cleared in kidney
Half-life: 24 hours
Neuropsychiatric side effects
Works better than bupropion or patch, but not both combined
Can't combine with nicotine
Comorbidity (nicotine)
People with certain psychiatric disorders, such as schizophrenia or affective disorders, are more likely to smoke