Effects of Nicotine on the Nervous System

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Questions and Answers

What effect does nicotine have on nicotinic acetylcholine receptors (nAChRs) following chronic exposure?

nAChR levels are upregulated (correct)

nAChR levels decrease sharply

nAChR levels remain unchanged

nAChR becomes less sensitive to other neurotransmitters

In terms of behavioral responses, how does nicotine affect motivation in rats?

Results in immediate tolerance to rewards

Increases variability in behavioral responses

Substitutes for cocaine by increasing dopamine release (correct)

Decreases overall activity levels

What is a key neurophysiological effect of acetylcholine (ACh) removal from the synapse?

Desensitization of the receptors due to nicotine (correct)

Prolonged activation of nAChRs

Enhanced synaptic transmission of ACh

Rapid resensitization of the receptors

After 7 days of exposure to nicotine, what change occurs in the Smooth Muscle Activity (SMA) related to nicotine's effects?

SMA increases after an initial decrease Signup and view all the answers

Which behavior is NOT influenced by nicotine according to the provided content?

Cognitive restructuring Signup and view all the answers

What behavioral response is observed in monkeys regarding nicotine infusion?

They show a preference for light preceding the nicotine infusion. Signup and view all the answers

How do humans self-administer nicotine infusions?

On a fixed ratio of 10. Signup and view all the answers

What is a significant peripheral nervous system effect of nicotine?

Increased gastrointestinal muscle contractions leading to diarrhea. Signup and view all the answers

What neurological effects are associated with nicotine on the central nervous system?

Increased arousal and EEG patterns similar to concentration. Signup and view all the answers

What is the approximate toxic dose of nicotine that can be fatal to children?

6 mg. Signup and view all the answers

Which effect is a result of low doses of nicotine?

Stimulation leading to hypertension and tachycardia. Signup and view all the answers

What subjective effect is reported after the rapid absorption of nicotine?

Peak ratings of 'high' after 4 minutes. Signup and view all the answers

What occurs during an overdose of nicotine?

Convulsions followed by respiratory failure. Signup and view all the answers

What effect does acidic urine have on the excretion of nicotine?

Increases excretion of nicotine Signup and view all the answers

What is the primary receptor type that nicotine stimulates in the central nervous system?

Nicotinic acetylcholine receptors Signup and view all the answers

What is the main physiological response when nicotine activates cholinergic receptors?

Opening of Ca+ and Na+ channels Signup and view all the answers

What is a common subjective effect experienced by inexperienced smokers after nicotine administration?

Nausea and vomiting Signup and view all the answers

How does chronic nicotine use affect cholinergic receptors over time?

Leads to increased receptor density and sensitivity Signup and view all the answers

What is the LD50 of nicotine?

60 mg Signup and view all the answers

What happens to heart rate when nicotine is consumed?

Increases by 10-20 beats per minute Signup and view all the answers

What effect does nicotine have on performance in attention-related tasks?

Increases accuracy in detecting targets Signup and view all the answers

What physiological effect does nicotine have on blood flow?

Decreases blood flow to the skin Signup and view all the answers

What happens during nicotine overdose?

Convulsions followed by respiratory failure Signup and view all the answers

Study Notes

Tobacco & Nicotine Overview

Tobacco is cultivated from Nicotiana tabacum and Nicotiana rustica.
Nicotiana rustica has a higher nicotine content (9%).
Nicotine is the most common substance found in tobacco products.

Tobacco & Nicotine History

Mayans used tobacco in Central America.
Tobacco was introduced to Europe in 1492 by Columbus.
Tobacco was initially referred to as "drinking smoke".
In 1559, Jean Nicot heralded medicinal properties, and named the genus.
Tobacco was smoked in hollow canes which led to cigarette inventions.
The first study connecting smoking with lung cancer was published in 1938.

Tobacco & Nicotine Regulations

Cigarette packages were labeled with warnings about health risks in 1966.
In 1994, the FDA argued that nicotine is addictive and manufacturers manipulated its delivery in tobacco products.
The 2009 Family Smoking Prevention and Tobacco Control Act put tobacco products under FDA control; regulating marketing and protecting public health.

Pharmacokinetics - Routes of Administration and Oral Administration

Oral administration is a significant factor in nicotine absorption.
Chewing tobacco and moist snuff absorb nicotine through mucous membranes in the mouth/cheek.
Nicotine absorption is influenced by the pH of the environment.
Nicotine is not well absorbed in acidic environments; extensive liver metabolism occurs.
Nicotine absorption often leads to vomiting after consumption as it's highly toxic.
Moist snuff creates saliva with pH 5.0 - 8.6.
Dip-chew 8 - 10 times a day equals roughly 30 - 40 cigarettes.

Pharmacokinetics - Inhalation

Inhalation is the most common route for nicotine entry into the human body.
Cigarettes contain acidic smoke that lowers saliva pH to 5.3.
Ionization of nicotine prevents mouth absorption, thus inhalation is crucial.
Nicotine dissolves in lung mucous; travels to the heart, then to the brain.
Nicotine absorption from cigarettes is significantly faster than intravenous injection.
Average cigarette contains 10-15 mg nicotine; 1.5 to 2.6 mg are absorbed per 10-15 puffs. Absorption varies based on smoking method.
Pipe and cigar smokers inhale less; alkaline smoke raises saliva pH to 8.5.
Most nicotine gets absorbed through buccal absorption, not inhalation.

Pharmacokinetics - Vaping

E-cigarettes aerosolize nicotine from cartridges containing propylene glycol, flavor, and nicotine.
15 puffs of an e-cigarette deliver 0.026 to 0.77 mg of nicotine.
Nicotine content varies in disposable and refillable cartridges (5–25mg).
Peak nicotine levels in blood range from approximately 6 to 19 ng/ml within 5 minutes or 15 puffs.
The rapid rise suggests nicotine absorption from the lungs.

Pharmacokinetics - Other Forms of Administration

Patch: slow build-up of nicotine, producing constant levels.
Gum: changing nicotine levels (similar to smoking behavior).
Nasal spray: cigarette-like effects; 3mg spray delivers approximately 4.7 ng/ml nicotine in the blood within 10 minutes.

Pharmacokinetics - Distribution

Nicotine enters the brain within 5 seconds of a single puff.
Maximal nicotine concentration is achieved within 1 minute.
Nicotine leaves the brain in 15 minutes and redistributes in organs like the liver, kidneys, salivary glands, and stomach.
Nicotine crosses the blood-brain and placental barriers.

Pharmacokinetics - Metabolism

The liver metabolizes nicotine into inactive metabolites (cotinine, nicotine-1'-N-oxide).
Smokers metabolize nicotine faster than non-smokers.
Nicotine's half-life is roughly 90-150 minutes (~2 hours).
Menthol slows down nicotine metabolism.

Pharmacokinetics - Excretion

Urine pH affects nicotine excretion.
Excretion is higher in an acidic environment.
30-40% of nicotine is excreted unchanged from the body.
Alkaline urine leads to less excretion, depending majorly on liver metabolism.

Neurophysiological Effects

Nicotine stimulates nicotinic cholinergic receptors (ionotropic receptors).
Activation opens Na+ channels, increasing permeability to Ca2+.
Chronic nicotine use increases the number and sensitivity of receptors.
This leads to withdrawal reactions and a heightened response to nicotine after waking.

Peripheral Nervous System Effects

Nicotine stimulates neuromuscular receptors resulting in tremors in heavy smokers.
Heart rate and blood pressure increase, harmful in patients with hypertension.
Blood flow to muscles and skin decreases; skin temperature lowered, with wrinkles and aging seeming quicker. Reduced ability to blush.
Nicotine causes gastrointestinal muscle contractions, leading to diarrhoea; in some cases acting as a laxative.

Central Nervous System Effects

Nicotine increases arousal, mimicking intense focus and concentration, based on EEG patterns.
This effect stimulates the RAS and induces respiratory stimulation.
Overdosing produces respiratory paralysis.
Nicotine can induce nausea and vomiting in inexperienced smokers, known as the "green around the gills" effect.
Nicotine enhances neurotransmitters like norepinephrine (NE) and dopamine (DA) in higher brain areas.

Toxic Effects

LD50 for nicotine is 60 mg.
Several fatal doses can be present in a single pack of cigarettes; however, absorption and elimination are effective.
Overdosing causes convulsions and respiratory failure.
A small amount of nicotine—6mg—can be fatal to children.
E-liquid refills contain a high concentration of nicotine; ingestion can be lethal to adults.

Subjective Effects

Individuals report feelings of "high" after 4 minutes/ 8 puffs from smoking, as plasma nicotine levels surge.
Nicotine levels spike after 6 minutes/ 12 puffs exceed 14ng/ml. Peak "high".
The pleasure associated with smoking is linked to rapid nicotine absorption, not sustained levels.

Performance Effects

40% of studies between 1994 and 2008 used nicotine-deprived smokers; their results likely are not valid as they were performance degraded by nicotine withdrawal.
These studies lack placebo controls and double-blind designs which make it difficult to rule out expectancy effects.
Nicotine enhancements in fine motor abilities (finger tapping and pegboard), speed and accuracy in continuous performance tests, alerting attention, orienting attention, and short-term episodic memory were observed in studies.

Harmful Effects - Heart Disease

Nicotine increases the workload of the heart and reduces oxygen transport, putting additional strain on the cardiovascular system.
Carbon monoxide (CO) from cigarette smoke lowers blood oxygen concentration. Other components in cigarette smoke negatively affect lungs by impacting oxygen absorption. Heart and lungs have to work harder to maintain oxygen levels in the body.

Harmful Effects - Lung Disease (COPD)

Cigarette smoke (ash and tar) coats the lungs, paralyzing cilia that remove pollutants, which increases susceptibility to infections.
In addition, the phagocytic elements in the lungs that attack harmful matter are also inhibited. Damaged lungs reduces airflow into and out of the lungs.

Harmful Effects - Cancer

Smoking is linked to 30% of all cancer-related deaths, with 23 times greater risk in male smokers and 13 times in females.
Quitting smoking significantly lowers the risk of lung cancer.

Harmful Effects - Reproduction

Smoking negatively affects fertility in individuals of both sexes.
Smoking affects sperm volume, sperm count, motility, and viability in males.
Females smokers are 1.7 to 3.2 times more likely to be infertile.
Smoking in pregnant women is associated with lower birth weights (LBW).

"Mind if I smoke? - Care if I die?"

Environmental tobacco smoke (ETS) affects non-smokers.
Mainstream smoke (MS) is exhaled by smokers.
Sidestream smoke (SS) is released during cigarette breaks between puffs.
The temperature of a cigarette's burning flame is markedly higher during mainstream smoke.
The concentration of carcinogens in sidestream smoke is greater than mainstream smoke.

Third-hand smoke

Toxic compounds from cigarette smoke can linger in homes and apartments.
These toxins persist for months after smoking.

Why do people smoke? - Constant Blood Level Theory

Attempts to maintain a stable nicotine blood level.
Changes in content of cigarettes affect smoking behaviors: Instead of increasing cigarette count, individuals change smoking practices (increased frequency/depth of puffs)
Nicotine levels are lowest after overnight periods of sleep and immediately increase after smoking, with 50% of smokers lighting up within 30 minutes.
Stress triggers acidification of the urine, causing increased nicotine excretion.
A drop in nicotine levels motivates individuals to smoke (especially when combined with external stress cues).

Nicotine Bolus Theory

Nicotine rapidly increases in blood and brain during inhalation (bolus).
The rapid release creates strong reinforcement and pleasure, explaining intense craving experienced by smokers.
The intense effect differs from other smoking methods. A bolus effect is not observed.

Dual Reinforcement Theory

Both nicotine and non-nicotine factors are essential for sustained smoking behaviors including environmental, sensory factors.
Sensory experiences associated with smoking act as rewarding (secondary) stimuli.
Sensory associated with smoking enhance the nicotine reinforcement effect. These stimuli maintain smoking behavior and relapse.

Withdrawal

Psychologically and physically stressful.
Ex-heroin users report it's harder to quit tobacco than heroin.
Symptoms include increased heart rate, increased food intake, difficulty concentrating, increased wakefulness, cravings, anxiety and depression.
Withdrawal symptoms appear within 1 to 2 days, peaking after 1 week, easing off after between 1-6 months.
Nicotine replacement therapies can alleviate these symptoms via taste, smell, or act of smoking a denicotinized cigarette.

Withdrawal - Severity

Withdrawal severity is unrelated to nicotine dose.
Nicotine metabolizing rate of individuals affects symptoms severity.
Fast metabolizers experience more severe withdrawal due to rapid reduction of nicotine levels.
Symptoms are associated with reduced dopamine in the nucleus accumbens (NAC).
This reduces reward system stimulation leading to anhedonia.

Treatment - Nicotine replacement therapies (NRT)

2/3 of adult smokers want to quit; 17 million try each year. Fewer than 1 in 10 succeed.
NRT effectiveness is around 10% with placebo after 6 months.
NRT effectiveness is around 17% with NRT after 6 months.

Treatment - E-cigarettes

Randomized, placebo-controlled studies demonstrate that e-cigarettes have reduced effectiveness toward complete smoking cessation.
Nicotine likelihood and addiction is increased in adolescents when exposed to e-cigarettes.
The increasing efficiency in nicotine delivery fuels the growing uptake of electronic cigarettes.

Treatment - Buproprion

Inhibits norepinephrine and dopamine reuptake, acting as an antidepressant (Sold as Zyban).
Reduces nicotine's reinforcing effects and withdrawal severity.
As effective as NRT with a combined effect on its own (OR= 1.9).
Potentially reducing post-smoking weight gain is a beneficial side effect.

Treatment - Varenicline

Partial nicotinic receptor agonist; produces a weaker effect than nicotine and blocks nicotine.
Sold as Chantix or Champix.
Alleviates nicotine withdrawal and blocks nicotine effects from smoking.
A 2006 Pfizer study demonstrated 23% of varenicline users achieve continuous abstinence within 1 year, while 15% quit on bupropion, 13% on NRT, and 10% on placebos.

Treatment - Behavioral & Vaccination

Group therapy has high effectiveness (OR 2.17) compared to pharmacological treatments.
Nicotine vaccines have been developed and are thought to prevent nicotine brain access.
However, current clinical trials have not successfully demonstrate their efficacy.

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Description

Explore the multifaceted effects of nicotine on nicotinic acetylcholine receptors and behavioral responses in various animals. This quiz delves into neurophysiological impacts, self-administration behaviors, and the consequences of chronic nicotine exposure. Test your knowledge on this critical substance and its implications for both peripheral and central nervous systems.