Chapter 8: Nicotine

Question 1

In terms of pka and lipid solubility, why is it ineffective to eat cigarettes? Why is it better to inhale cigarettes for max effect?

Answer 1

cigarette smoke is FLU CURED and when it is dissolved in the saliva, it makes the solution acidic, ionizing the nicotine moleucles. The nicotine cannot get absorbed into the lipid bucal membranes because it is ionized and thus absorption is decreased. It is more effective to inhale cigarettes where pH has no effect on absorption in the lungs.

Question 2

Why can air cured tobacco be absorbed in the mouth rather than flu cured tobacco?

Answer 2

because air-cured tobacco makes saliva basic rather than acidic. the nicotine will not be ionized at that pH and thus the nicotine from the air-cured can still pass into the blood stream (still get absorbed)

Question 3

Nicotine that is absorbed rapidly from the lungs creates a nicotine _____; and gets to the brain rapidly in large doses, something that does not happen if nicotine is slowly absorbed from nose or mouth capillaries

Answer 3

Nicotine that is absorbed rapidly from the lungs creates a nicotine BOLUS ; and gets to the brain rapidly in large doses, something that does not happen if nicotine is slowly absorbed from nose or mouth capillaries

Question 4

In the mouth, Nicotine is absorbed through the ___ membranes

Answer 4

buccal membranes

Question 5

why is eating nicotine not very effective?

Answer 5

because nicotine is a weak base with a pka of 8 and will not have many lipid soluble molecules at pH 6 or lower; most of the nicotine will be ionized. The nicotine will not be readily absorbed through the acidic digestive system, and is also subject to FIRST PASS METABOLISM in the liver before entering the blood stream and getting to the brain.

Question 6

T/F gum, lozenges and patch produces a bolus in the brain

Answer 6

False; gum, lozenges and the patch do not form boluses, but gum and lozenges do provide rapid absorption, whereas patch is slow absorption of nicotine

Question 7

Comment on the absorption affects of inhalers and nasal spray

Answer 7

inhalers and nasal spray do not form boluses in the mucus membranes of the mouth and nose, but they do form boluses when the substance moves to the lungs.

inhalers provide slow absorption whereas nasal sprays provide fast absorption of nicotine.

Question 8

2 inactive metabolites that nicotine is broken down into

Answer 8

1) conitine

2) nicotine-1-n-oxide

Question 9

What kind of urine (acidic or basic) will facilitate reabsorption of nicotine in the kidneys? facilitate excretion?

Answer 9

Acidic urine will facilitate excretion because nicotine will be in ionized form, making it not as lipid soluble and thus will be peed out.

basic urine will increase reabsorption in the blood because more nicotine will be lipid soluble and not ionized, thus being able to cross back into the blood stream.

Question 10

Why is it that experienced smokers exhibit lower brain levels of nicotine than non-dependent smokers under similar administration conditions and same dose?

Answer 10

because experienced smokers have better nicotine metabolizing systems. They have METABOLIC TOLERANCE and can metabolize nicotine faster than non-smokers.

Question 11

What’re the two cholinergic receptors? which receptor does nicotine act on?

Answer 11

1) muscarinic

2) nicotinic: nicotine acts on the nicotinic cholinergic receptor.

Question 12

What do nicotinic cholinergic receptors do in the PNS? how is this blocked? what do nicotinic cholinergic receptors do in the CNS?

Answer 12

Nicotinic cholinergic receptors in PNS: act as NEUROMUSCULAR JUNCTIONS of striated muscles and control voluntary muscle action. This can be blocked with Curare, which causes muscle paralysis.

in CNS: nicotinic cholinergic receptors are generally ionotropic and regulate ion channels. When an agonist (acetylcholine or drug) binds to the nicotinic cholinergic receptor, the pore opens and allows flow of Na+ and K+ into the cell, creating a PSP

Question 13

When a nicotinic cholinergic receptor is located on a PRE-synaptic neuron, what happens to the neurons ability to release neurotransmitters when an agonist is present? why?

Answer 13

When a nicotinic cholinergic receptor is located on a PRE-synaptic neuron, an agonist INCREASES THE PERMEABILITY TO CA2+ IONS, allowing the RELEASE OF MORE TRANSMITTERS.

Question 14

nACHRs are involved in ____ when located POST synaptically, and act as _____ when located presynaptically

Answer 14

nACHRs are involved in EXCITATORY POST SYNAPTIC TRANSMISSION (EPSPs) when located POST synaptically, and act as NEUROMODULATORS when located presynaptically (allows the release of more or less transmitters by dictating the permeability of Calcium ions)

Question 15

Describe the three receptor configuration states of a nACHr

Answer 15

1) basal state: AChR receptor has HIGH affinity for antagonists and thus the ion channel is closed
2) Active state: channel is OPEN
3) desensitizes state: ion channel is closed; occurs when there is too much agonist (the receptor is “tired” or “fried”)

Question 16

nACHR enters ____ configuration when an agonist, like nicotine or Ach), binds to an ___ subunit, causing the ion channel to open.

Answer 16

nACHR enters ACITIVE configuration when an agonist, like nicotine or Ach), binds to an ALPHA subunit, causing the ion channel to open.

Question 17

nAChR enters____ configuration when an agonist leaves, causing the ion channel to close.

Answer 17

nAChR enters BASAL configuration when an agonist leaves, causing the ion channel to close.

Question 18

nAChR enters the ____ state when the receptor site is repeatedly activated and is not receptive to agonists or antagonists.

Answer 18

nAChR enters the DESENSITIZED state when the receptor site is repeatedly activated and is not receptive to agonists or antagonists.

Question 19

which configuration state is responsible for acute tolerance of nicotine?

Answer 19

change to desensitized state may be an explanation for acute tolerance. When you first administer the drug, the nACH receptors are stimulated and enter the active state, but after prolonged duration of the drug being in the system, the nAChr may enter desensitized state and will no longer be stimulated.

Question 20

When does upregulation of nACh receptors occur? How does this relate to the withdrawal symptoms of nicotine?

Answer 20

when a high concentration of agonist (nicotine or Ach) cause nAChR receptors to stay in their desensitized state for long periods of time. When someone cuts back on the nicotine consumption, the agonist concentration decreases and their is an excess of highly sensitive AchR receptors that are no longer in their desensitized state, causing incresed firing, increased response to nicotine once the person smokes again (ex/ in the morning after a period of nicotine fasting via sleeping) and withdrawal effects of nicotine.

Question 21

What can block nAChRs in the PNS? in the CNS?

Answer 21

Curare blocks nAChrs in the PNS at neuromuscular juntctions, causing paralysis

Mecamylamine blocks (is an antagonist) neuronal nAChR’s.

Question 22

Why may nicotine at high doses be lethal due to respiratory paralysis?

Answer 22

at high doses, nicotine will push the receptors into desensitized state, making them not react to any sort of stimulation.

Question 23

What system does the nicotine act on in order to cause tremors?

Answer 23

at low doses, nicotine acts on the PNS and acts on the nACHrs located on the neuromuscular junctions of striated and voluntary muscles/

Question 24

The autonomic parasympathetic nervous system is typically _____, blocking AChr receptors to help control glands and involuntary muscles.

Answer 24

the autonomic parasympathetic nervous system is typically ANTICHOLINERGIC

Question 25

Is nicotine biphasic?

Answer 25

yes. it can stimulate and inhibit transmission of autonomic ganglia as nicotinic receptors enter the desensitized state.

Question 26

What other neurotransmitter is released due to the presence of nicotine? what does this cause?

Answer 26

epinephrine is also released due to the presence of nicotine because nicotine can act as a neuromodulator and open up a cells calcium channel, causing it to release more of its neurotransmitter, in this case, epinephrine. this produces stimulation of the SYMPATHETIC NERVOUS SYSTEM (fight or flight mode), causing vasoconstriction of skin, increased heart rate and blood pressure. the epinephrine also arouses the CNS.

Question 27

alpha 2 and 4 and beta 2 mediate nicotine ____, whereas alpha 3 and 5 and beta 4 create ______ to nicotine

Answer 27

alpha 2 and 4 and beta 2 mediate nicotine REINFORCEMENT, whereas alpha 3 and 5 and beta 4 create AVERSIVE EFFECTS to nicotine

Question 28

mice that do not have the gene to code for beta 2 subunits tend to ____ Like/dislike nicotine because there is not as much dopamine release.

Answer 28

mice that do not have the gene to code for beta 2 subunits tend to DISLIKE nicotine because there is not as much dopamine release.

Question 29

mice WITH beta 2 subunit gene of the nACh receptors like nicotine because:

Answer 29

because there is increased dopamine activity– beta 2 subunits may play a role in pleasure conveyance.

Question 30

T/F a person who has alpha 5 in their AChr receptors will administer more nicotine than a person who does not have alpha 5 subunits

Answer 30

false. alpha 5 subunit containing ACh receptors are associated with DECREASED DOPAMINE RELEASE and therefor people with the alpha 5 subunit are more likely to exhibit aversive effects of nicotine.

A person with NO ALPHA 5 subunit is at higher risk for being a smoker because they LIKE NICOINE. THEY DO NOT EXHIBIT AVERSIVE EFFECTS BECAUSE THEY DO NOT HAVE AN ALPHA 5 SUBUNIT.

Question 31

increase the reward threshold indicates that ____ substance is required for the person to feel happy or rewarded, meaning that there is a decrease in brain reward function (reward system is not functioning as well)

Answer 31

increasing the reward threshold indicates that MORE substance is required for the person to feel rewarded/ more substance is required to cross the threshold.

Question 32

typically, nicotine induces _____ of ICSS reward thresholds, enhancing the reward value of other simuli.

Answer 32

typically, nicotine induces lowering of reward thresholds, ENHANCING the reward value of other stimuli

Question 33

a nicotinic receptor antagonist, 4-nitroPFEB _____ nicotine-induced lowering of reward thresholds

Answer 33

a nicotinic receptor agonist, 4-nitroPFEB completely blocks nicotine-induced lowering of reward thresholds- nicotine will no longer lower the threshold and thus will no longer enhance reward values of other stimuli

Question 34

Why do nicotinic receptor anatagonists block nicotine self administration?

Answer 34

nicotinic receptor antagonists no longer allow nicotine to reduce reward thresholds, thus, individuals with nic-receptor antagonists will not experience as large of pleasureable effects (less dopamine).

Question 35

How does GABAb agonism effect nicotines ICSS thresholds?

Answer 35

GABA AGONISM blocks nicotine-induced REDUCTION on ICSS thresholds, indicating a prevention of increased dopamine release

Question 36

How does NMDA Antagonism affect nicotines ICSS thresholds? What does this say about nicotines relationship with the glutaminergic system?

Answer 36

NMDA antagonisms REVERSES nicotine-induced lowering of ICSS thresholds. ICSS thresholds literally increase when an NMDA antagonist is present. This indivates that the person is not experiencing as much pleasureable effects with hte same dose as nicotine as they used to be, because their reward thresholds are higher. The fact that NMDA antagonism reverses the effects of nicotine indicates that glutamate has a relationship with nicotine and that nicotine creates reinforcing effects with the help of glutamate.

Question 37

T/F non smokers do not report enjoyment of nicotine

Answer 37

true. smokers may like nicotine more because they are either tolerant to the aversive effecsts, or they are increasingly sensitive to rewarding actions of nicotine (recall, nicotine lowers a person’s reward thresholds)

Question 38

In terms of performace, nicotine _____ accuracy and ____ speed of identification of an object. This was tested either by the _____ or the _____test.

Answer 38

In terms of performace, nicotine DOES NOT IMPROVE accuracy, but ENHANCES speed of identification of an object. This was tested either by the CHOICE REACTION TEST or the DISTRACTION test.

Question 39

What is episodic memory?

Answer 39

memory for events times and places.

Question 40

how does nicotine affect episodic memory in terms of short term and long term episodic memory??

Answer 40

nicotine improves SHORT TERM episodic memory but not LONG TERM episodic memory

Question 41

What is the nback test and what kind of memory does this measure? How does nicotine influence this type of memory?

Answer 41

the nback test is when participants are presented with a visual display of constantly changing letters in which the target letter appears. Then the participants are asked to report which letter had been presented immediately before, 2 letters before, 3 letters before, “n” letters before. This tests WORKING MEMORY. nicotine has a NEGATIVE effect on WORKING MEMORY ACCURACY but POSITIVE effect on SPEED OF WORKING MEMORY

Question 42

Typically, nicotine has ____ effects on speed of alerting/ orienting attention and working memory, and ____ effects in accuracy of attention/ long term episodic memory or working memory

Answer 42

Typically, nicotine has POSITIVE effects on speed of alerting/ orienting attention and working memory, and NEGATIVE effects in accuracy of attention/ long term episodic memory or working memory

Question 43

cognitive benefits and decreased prepulse inhibition (why schizophrenics smoke) associated with nicotine is most likely due to the reversal of _____

Answer 43

hypofrontality

Question 44

How is nicotine similar to amphetamines?

Answer 44

• they are both dosage dependent: high doses suppress motivation behavior and low rates enhance motivation behavior
• nicotine does not increase responses that have been suppressed by punishment
• both increase activity in catecholamine synapses (dopamine, epinephrine, acetylcholine)

Question 45

What proof is there that nicotine will not be good for ADHD treament? (even though stimulants like ampheatmines are used to treat ADHD)

Answer 45

Nicotine seems to disrupt the ability to withhold response on a differential of low rates schedule- nicotine even at the lowest dose causes rats to respond too soon to get a reward. this is not ideal for individuals with ADHD as they are supposed to learn how to inhibit their responses

Question 46

Why is cocaine and nicotine generalization bi-directional?

Answer 46

because nicotine will generalize completely to cocaine, but cocaine will not generalize to nicotine in rats

Question 47

How can stimulus and cue properties of nicotine be blocked? which nervous system is involved in blocking stimulus and cue properties?

Answer 47

by mecamylamine, and NAChR antagonist. Nicotine’s effects and detection can only be blocked by the CNS, NOT BY CURARE IN THE PNS

Question 48

T/F nicotine will generalize to caffeine and other stimulants

Answer 48

false. but nicotine can act as a cue

Question 49

____ blocks nicotine discrimination, where as ____ potentiates nicotine discrimination

Answer 49

ALCOHOL blocks nicotine discrimination, where as CAFFEINE potentiates nicotine discrimination

Question 50

which brain structure is reponsible for mediating the discriminative properties of nicotine?

Answer 50

the cortex

Question 51

T/F severity of nicotine withdrawal symptoms are related to how long a person has smoked for

Answer 51

FALSE. the withdrawal symptoms are related to how fast a person can metabolize nicotine. The faster nicotine is metabolized, the more severe the withdrawal.

Question 52

In terms of ICSS, how does cigarette quitting contribute to a person’s state of ahedonia?

Answer 52

A person who stops smoking reverse the nicotine-induced lowering of ICSS. therefore, there is an INCREASED threshold for the rewarding effects of electrical brain stimulation, indicating a DEPRESSION in the reward system and thus LESS DA IN THE NUCLEUS ACCUMBENS. The suppression of the reward system= not as happy = depression = decrease in motivation to engage in normally pleasurable activities.

Question 53

In terms of ICSS, how does cigarette quitting contribute to a person’s state of ahedonia?

Answer 53

A person who stops smoking reverse the nicotine-induced lowering of ICSS. therefore, there is an INCREASED threshold for the rewarding effects of electrical brain stimulation, indicating a DEPRESSION in the reward system and thus LESS DA IN THE NUCLEUS ACCUMBENS. The suppression of the reward system= not as happy = depression = decrease in motivation to engage in normally pleasurable activities.

Question 54

T/F : nicotine has a wide range of reinforcement doses

Answer 54

false. Nicotine has a narrow dose range. too low a dose = non reinforcer, too high a dose= adverse effects of nicotine

Question 55

The reason why too high a dose of nicotine does not have reinforcing effects is because adverse effects are seen. Why is this the case?

Answer 55

because the medial habernula is stimulated. the medial habernula in the brain has more alpha 5 subunits in their nACh receptors, which create adverse side effects.

Question 56

What type of schedule is best to use if you want to see nicotine responses?

Answer 56

2nd order schedules.

Question 57

4 theories as two why humans self administer nicotine

Answer 57

1) constant blood level theory: people avoid withdrawal by maintaining a constant level of blood nicotine
2) nicotine bolus theory: people smoke for the reinforcing effect of the nicotine bolus (high concentration of nicotine) that hits the brain after each puff, resulting in enhanced activation of nAChRs, high amounts of dopamine release, etc.

3) Psychological tool theory: people use nicotine as a tool to moderate their arousal level. Raises arousal when bored, lowers arousal when stressed, improves cognitive and motor tasks
4) Dual reinforcement model: primary reinforcement of dopamine use arises from nicotine’s effect on the mesolimbic dopamine system, and the secondary reinforcement effect is caused by the taste and smell of tobacco, which is PAIRED to the primary reinforcer.

Question 58

What is nicotine replacement therapy

Answer 58

when nicotine is administered an alternative route such as a patch or IV.

Question 59

Describe how bupropion helps treat nicotine withdrawal

Answer 59

it is an antidepressant. Nicotine withdrawal creates decreased amounts of dopamine, causing depression. bupropion prevents dopamine reuptake, which helps concentrate dopamine in the synapses, reducing depression and decreasing chances of relapsing.

Also, it is an alpha4 beta 2 subunit-nAChR antagonist. Recall, these subunits play a role in increasing reinforcing effects. by blocking nAChR receptors, bupropion diminishes the primary reinforcing effects of nicotine.

Question 60

How does champix/varencline help treat nicotine withdrawal?

Answer 60

it attaches to the nAChr receptors itself, creating some nicotine primary affects, but also precents nicotine from binding. It also is a serotinin reuptake blocker, which contributes to the reduction in feelings of depression

Question 61

How does nicQB or TA-nic work?

Answer 61

it is an immunization which makes your body create antibodies for nicotine, blocking nicotine from entering the blood brain barrier. thus you do not get the primary reinforcing effects of nicotine when you smoke.

Question 62

How does mecamylamine work as a treatment in nicotine withdrawal?

Answer 62

it is a nicotine receptor blocker, thus nicotine has less effects.