Nicotine

1
Nicotine

• Danielle Lissner
• Kayla James
• Kim Pettijohn

2
Nicotine History

• Two types of tobacco plants
• Nicotiana tabacum
• Nicotiana rustica
• Use became popular in Europe and US in mid-19th
  century
• New methods of curing leaves
• Cigarette machine

3
Pharmacology and Relationship to Smoking

• Nicotine 6-11 mg per cigarette
• Enters lungs on tar mixture of hydrocarbons
  known to be carcinogenic
• Smoking is quickest and most efficient way to get
  nicotine to the brain
• Reinforcing effects are strongest
• 70-80 is transformed into cotinine by cytochrome
  P450 2A6 (CYP2A6)
• Some people have low CYP2A6 activity-reduced
  nicotine metabolism

4
Pharmacology Contd

• Half-life of nicotine is about 2 hours
• Mild withdrawal during overnight and tolerance
  from previous day partially dissipates
• Strong craving and best response in the morning
  (1st cigarette)

5
Mechanisms of Action

• Nicotinic cholinergic receptors
• Ionotropic
• Only a and ß subtypes
• High affinity in cerebral cortex, thalamus,
  striatum, hippocampus, substantia nigra, ventral
  tegmental area, locus coeruleus and the raphe
  nuclei
• Found in ganglia of Autonomic Nervous System
• When binds it opens a Na channel and depolarizes
  the cell membrane
• Sometimes allows Ca2-dependent second messenger
  functions

6
Behavioral and Physiological Effects

• Nicotine increases calmness and relaxation
• Relief of withdrawal symptoms
• Nicotine enhances performance in cognitive tasks
• Attentional demands
• In smokers and non-smokers
• Effects on EEG activity

7
Physiological Effects Contd

• Sympathetic
• Adrenal glands release epinephrine and
  norepinephrine
• Increased heart rate and elevated blood pressure
• Parasympathetic
• Hydrochloric acid secretion in stomach
• Chronic diarrhea
• Colitis
• Body weight

8
Animal Studies

• Marina Picciotto (1997)
• Nicotine injection
• Sustained attention and working memory
• ß2 knockout mice
• Self-administration
• Rats, mice, dogs and primates
• Adolescent v. adult exposure

9
Reinforcing Effects

• Mediated by activation of mesolimbic dopamine
  system
• High-affinity nicotinic receptors located in the
  VTA stimulate the firing of dopaminergic neurons,
  which causes increased DA release in the NA
• ß2 subunit

10
Nicotine Is a Toxic Substance

• 60 mg
• Nicotine poisoning
• Accidental swallowing
• Excessive absorption
• Exposure to pure nicotine
• Symptoms

11
Tolerance

• Acute tolerance
• Short-lived
• Chronic tolerance
• Long-term exposure
• Gehlbach et al (1974)
• Mecamylamine
• Receptor antagonist
• Injections in VTA produces reduced DA release in
  accumbens and withdrawal symptoms.

12
Cigarettes

• Trends in Smoking
• Lung cancer (1950s)
• Filtered cigarettes
• Surgeon General (1964)
• Ads and Taxes
• Still smoking?
• Male vs. Female

13
Stressing or Relaxing?

• Nicotine Resource Model

• Deprivation Reversal Model

• Two Advantages
• Mood control stress reducer
• Concentration enhancement

• Smoking causes stress
• Between cigarettes
• Must smoke more
• To counter the stress
• Researchers agree with this model the most

14
So Why Smoke?

• Nicotine
• Brands containing low nicotine
• Abstinence symptoms
• Nicotine gum
• Other factors
• Sensory stimuli
• CS gt secondary reinforcers

15
Illness and Death

• Major preventable cause of death
• Cancer
• Cardiovascular disease
• Respiratory disease
• Low birth weight
• Nicotine Replacement
• 1. treat the withdrawal symptoms
• 2. maintain a level nicotine
• 3. safer ways to obtain nicotine (chewing gum)