Neurology 342 -- Low Efficacy Stimulants: Nicotine

psychoactive component of tobacco

What is nicotine?

- buccal(chew)

- oral

- patches

- inhalation

What are the different routes of administration of nicotine?

inhaled by a smoker

What is firsthand smoke?

exhaled by a smoker and you inhale it

What is secondhand smoke?

toxic residue that sticks to surfaces and dust after smoke clears

What is third hand smoke?

lipid soluble and readily absorbed by the body

What are characteristics of nicotine absorption

cigarette: 6-11mg

- blodstream: 3mg

How many mg of nicotine does a cigarette have and how much reaches the bloodstream?

pH dependent

nicotine absorption is dependent on what?

smokking/vaping

What ways allow for the fastest absorption of nicotine?

BBB

nicotine is permeable to what barrier?

7-20 seconds

how long does it take to reach the brain?

CYP2A6

Nicotine is metabolized in the liver by what enzyme?

cotinine

what is nicotine's active metabolite?

women

who has faster metabolism of nicotine men or women?

menthol

What inhibits CYP2A6 activity(makes it slower)?

- urine

- breast milk

What are ways of excretion of nicotine?

~ 2 hrs

What is the half life of nicotine?

ACh system

nicotine and cotinine interact w/ what system?

cell bodies in basal forebrain and projects to cerebral cortex/ limbic system

the ACh system has cell bodies located where and projects to where?

- attention

- learning

- memory

What are the functions of the pathway from the basal forebrain to cerebral cortex?

choline and acetyl CoA

What are the two precursor to make ACh?

choline acetyltransferase

What enzyme is used to combine choline and acetyl CoA?

acetylcholinesterase

What breaks down ACh?

full agonist

- cause influx of + ions into neuron

nicotine acts as what @ nicotinic ACh receptors(nAChR)?

- persistent activation of nAChRs

- continuous depolarization of postsynaptic cell

What does high doses of nicotine lead to?

cannot fire again until nicotine is removed from receptor

Since the postsynaptic neuron is "stuck" because of the high doses of nicotine what happens to it?

depressant action

The high doses of nicotine produce what type of action?

mesolimbic DA pathway

Which pathway is important for the reinforcement aspects of nicotine?

increase DA release into nucleus accumbens

as nicotine binds to nAChR in the VTA what does this cause?

cause arousal, anxiety dizziness and nausea

What type of behavioral effects does nicotine produce in non-smokers?

produce calm or relaxed state

What type of behavioral effects does nicotine produce in smokers?

xxx

What are the acute effects of nicotine?

learning, memory, and attention

What are the benefits of nicotine?

- ADHD

- Tourette's syndrome

Nicotine reduces symptoms in?

increase capacity for learning verbal material after use of nicotine

What is the relation between nicotine and patients w/ Alzheimer's disease?

- lower incidence of Parkinson's disease

- neuroprotective for dopamine neurons

What is the relation between nicotine and patients w/ Parkinson's disease?

dependence and tolerance

Chronic exposure to nicotine induces what?

down regulation of nAChR

chronic nicotine uses cause what to nicotinic acetylcholine receptors?

increased smoking

- progresses to physical dependence

The development of tolerance to nicotine leads to what?

body expects and "needs" substance to avoid unpleasant withdrawal effects

What is physical dependence?

abstinence syndrome

Name the term for the long withdrawal that leads to a complex ____?

- affective symptoms

- somatic symptoms

- cognitive symptoms

What are the 3 subcategories of nicotine withdrawal symptoms?

cognitive symptom

Which nicotine withdrawal symptom includes difficulty concentrating and impaired memory?

Affective syndrome

Which nicotine withdrawal symptom includes anxiety, irritability, anhedonia, and insomnia?

somatic symptoms

Which nicotine withdrawal symptom includes tremors, bradycardia, hunger, and weight gain?

- resensitization of nAChRs

- return of normal levels of nACHr

How is abstinence syndrome mediated?

habenula

nicotine withdrawal leads to hyperactivity of what brain region that shuts down the mesolimbic DA system?