Nicotine

Oral administration of nicotine

slowly absorbed, experiences first pass metabolism, 1/3 potency of smoking but induces vomiting

administration via inhalation

90% goes to lungs, then heart and brain

amount absorbed depends on smoke and pattern of inhalation

distribution of nicotine

leaves brain after 15-30 min, goes to liver, kidneys, salivary glands, stomach

crosses all barriers

excretion of nicotine 

kidneys (urine), liver (2 different metabolites) 

half life varies from 90-150 min

little daily accumulation but depends on bedtime smoking 

2 types of cholinergic receptors

Muscarinic, Nicotinic

Nicotinic receptors

inotropic, stimulated by nicotine at low doses, at high doses blocked by nicotine

can take 3 configurations: basal, active, desensitised state 

nicotinic receptors are located in the

PNS and CNS

releases serotonin, dopamine, noradrenalin, causing pleasure and arousal and autonomic responses

Brain stem effects

reflex inhibition

midbrain effects

release of noradrenaline and dopamine = antidepressant effects

Nesbitt’s Paradox

increased arousal but decreased stress

physiological effects on animals

decreased SMA then increases post tolerance

Conditioned responses in humans

reinforcing, want to maintain constant nicotine level - bolus, situation factors, dual reinforcement (conditioned cues enhance reinforcement)

increases conditioned behaviour, disrupts shock-avoidance

self administration in animals 

animals don’t self administer but monkeys can be made dependent thorough forced consumption

Discrimination

0.2mg/kg - partially generalizes to amphetamines and coke

nicotine withdrawal

appears over first 3 days, peaks 1 week, disappears over a month

cravings, severity dose and length dependent

Nicotine replacement therapies include

patches, gum, nasal spray

Bupropion (Zyban)

increases dopamine and NE while weakly blocking nicotinic receptors

Varenicline (Champix)

mild dopamine stimulation and nicotine blockade at receptor

Nicotine vaccination 

stimulate bodies immune system to create antibodies which block nicotine from crossing BBB