Exam 2: Nicotine Pt. 2 Flashcards
nicotine is an agonist for…
nicotinic acetylcholine receptors (nAChR)
- binds to same place as Ach
- opens Na ion channels, excitatory response - depolarization
- high affinity receptors in brain and autonomic ganglia
high doses of nicotine lead to persistent activation of …
nAChR and continuous depolarization of postsynaptic cell
what is it when the cell cannot fire again until nicotine is removed
depolarization block
acetylcholine actions of a new smoker
Ach actions increase following nicotine use
- no pharmacodynamic tolerance yet
acetylcholine actions of an addicted smoker
brain compensates for amount of Ach by DECREASING the number of postsynaptic receptors (down regulation - form of pharmacodynamic tolerance)
nAChRs found both presynaptically and postsynaptically, facilitate actions of what?
ACh, dopamine, serotonin, and glutamate
- has effects on CNS, PNS, heart and other organs
nicotine activates sympathetic and parasympathetic systems causing…
wide range of physiological effects like tachycardia, and inc BP
MAO in smokers
smokers have way less MAO
- MAO breaks down monoamines like dopamine and norepinephrine
- if not broken down, these are remaining in the synapse for longer
inhibition of MAOs contributes to reinforcing effects of smoking
how does smoking affect the brain?
- alters the number of receptors available (up/down regulation)
- high affinity nAChR in the VTA stimulates firing of dopamine neurons which inc dopamine release in nucleus accumbens
when nicotine binds you get more action potentials so….
dopamine levels inc in the nucleus accumbens
what subunits are involved in nicotine reinforcement
a4, a6, B2
what is linked to the subjective effects of smoking, smoking rates, and the risk of developing nicotine dependence
genetic polymorphisms for a4, a6, B2
more receptors-more likely to be pleasurable
which subunits are involved in nicotine’s aversive properties - reducing the propensity to consume or self-administer
a5,a3,B4
where are nAChRs that mediate nicotine aversion concentrated
medial habenula to the interpeduncular nucleus
effects of nicotine: dopamine
pleasure, reward
effects of nicotine: norepinephrine
arousal, appetite suppression
effects of nicotine: acetylcholine
arousal, attention and cognitive enhancement (learning, memory)
effects of nicotine: glutamate
learning, memory improvement
effects of nicotine: serotonin
mood, appetite suppression
effects of nicotine: B-endorphin
reduces anxiety and tension
effects of nicotine: GABA
reduced anxiety and tension
4 benefits of nicotine
- learning, memory, ability (positive influence on cognition and motor function even in nonsmokers)
- symptoms reduced in ADHD and Tourette’s (tics)
- Alzheimer’s disease (patients see Ach neurons die, but with nicotine they have inc capacity for learning verbal material - replaces the lost Ach input)
-PD: dopamine neurons die, with nicotine they have lower incidences of PD
(nicotine is neuroprotective for dopamine neruons)
nicotine effects in smokers
- calm, relaxed state
- partly a relief from nicotine withdrawal symptoms
nicotine effects in nonsmokers
elicits heightened tension or arousal
lightheadedness, dizziness, nausea
-here Ach is acting as a true stimulant
acute effects of nicotine (7)
- general stimulant/arousal effects (inc HR and BP, alertness, appetite suppression)
- carbon monoxide reduces O2 transport to heart and organs
- calming (anxiolytic) effects in some (common users)
- mild euphoria
- cognitive enhancements
- antidepressant effects - dec in MAO
nicotine addiction cycle (6 steps)
- cigarette smoking
- nicotine absorption
- arousal, mood modulation, pleasure
- tolerance and physical dependence
- drug abstinence produces withdrawal symptoms
- craving for nicotine to self-medicate withdrawal symptoms
during the night, mild withdrawal occurs, but at the same time tolerance from the previous day dissipates
acute tolerance
acute tolerance is related to _____
desensitization of central nAChRs - including ones that mediate nicotine reinforcement `
chronic tolerance to nicotine
- long term exposure
- compensatory response in brain: upregulation of high affinity nAChRs
- subjective nicotine effects occur with frequent use
- slow to dissipate even after abstinence - nACR desensitization to blame
what leads up to chronic tolerance?
wanting, craving, needing
abstinence syndrome
long nicotine withdrawal
symptoms: affective, somatic, cognitive
affective symptoms of nicotine withdrawal
anxiety irritability depressed mood anhedonia (no longer find joy in things) insomnia restlessness hyperaglesia (inc pain response)
somatic symptoms of nicotine withdrawal
tremors bradycardia nausea respiratory changes hunger and weight gain
cognitive symptoms of nicotine withdrawal
difficulty concentrating (attention issues) impaired memory -changes in activation of frontal lobe
when do symptoms of abstinence syndrome subside
first few days is the worst, goes away within 2-4 weeks
what prevents withdrawal symptoms of nicotine
use of nicotine gum, transdermal patches, losenges give low doses so you do not get a rush or reward
abstinence syndrome is mediated by a combination of… (4 things)
- resensitization of the desensitized and up-regulated nAChRs (remove depolarization blocks)
- reduced activity of mesolimbic dopamine pathway
- increased CRF in amygdala (antireward system)
- activation of pathway between medial habenula and interpeduncular nucleus (nicotine aversion/side effects)
why do people smoke?
development and maintaining vaping and smoking habits
- to deliver nicotine to the body
- to keep taking it to maintain steady state
secondary reinforcers
conditioned stimuli
signal reward is coming
ex: that blue hoodie you always smoke in
nicotine resource model
smokers routinely report smoking causes relaxation, alleviation of stress, increased ability to concentrate
deprivation reversal model
positive effects of smoking represent alleviation of irritability, stress, poor concentration experienced by smokers between cigarettes
the “relaxing” effect of smoking almost brings the smoker to the ______ as a typical nonsmoker
same state
homeostasis
epigenetics of smoking
- when you are a chronic smoker, changes in over 1000 genes - if parents smoked this could impact your gene expression: memory, mood, how rewarding a drug is, birth defects, and immune system changes
- the environment changes what genes are active
smoking in pregnancy
- can pass through placental barrier - can effect fetus and brain
long lasting deleterious effects on somatic (motor, autonomic, social interactions), and neural behavior development
-dec in birth weight, dec in IQ, heart issues
adolescent smoking effects the…
PFC!!!!
- attention defecits, impulsivity, inc self administration of abused drugs
underdeveloped PFC until 25
