Nicotine

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How much does the UK government spend on treating tobacco related illness?
1.7 million
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What does Nicotine constitute?
0.6-3% of dry weight of tobacco with biosynthesis taking place in the roots, accumulating in the leaves
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How does Nicotine function?
Antiherbivore chemical as neurotoxin with particular specificity to insects therefore nicotine was widely used as an insecticide in the past
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Wha does an average cigarette yield?
103mg of absorbed nicotine, which is a fraction of the amount contained in a cigarette
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What does the absorbtion of nicotine across lungs alveoli depend upon?
attached tar molecules which makes the acidity suitable for such absorption
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What does pure nicotine in inhalators have?
To be at an extremely high dose to achieve the same level of absorbtion as a cigarette
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What does this have difficulty in?
replicating the fast, spiked absorption profile of cigarettes has proved to be a significant hurdle for the nicotine replacement industry
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What is the percentage of people that become addicted?
31.9%
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How many people are nicotine dependent according to DSM criteria?
60%
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How many people are long term low rate smokers?
10%
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What is the conclusion?
Tobacco dependence is not inevitable consequence of exposure to tobacco but an interaction between exposure and individual vuluerability
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Who is more likely to smoke?
Males
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What is shown in adolescent rats?
They are more likely to smoke when given the opportunity to self administer nicotine, adolesent rats worked harder for nicotine and took larger amount of nicotine than adults
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What is the conclusion?
Adolescents are vulunerable to nicotine addiction
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What was shown by Gourlay and Benowitz?
Arterial nicotine rose more rapidly and reached a higher peak
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What does nicotine primarily act upon?
brain cholinergic pathways, broadly distributed with cell bodies
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What are these clustered in?
The nucleus basalis and the pedunculopontine nucleus
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Wht is the nucleus basalis?
Regulate global function in the cortex such as attention, arousal, motivation, memory and consciousness
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What is the pedunculopontine?
In the brain stem, regulates level of arousal, motivation, processing of incoming information
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What does nicotine have?
The correct molecular shape to usurp Ach function by action on the same receptors (called nicotinic cholinergic receptors for this reason
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What is ACh?
A neuromodulator which can influence activity in target cells over long periods
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What does ACh play a role in?
Learning and intellectual function; degeneration in this system as seen in Alzheimer's disease
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What happens to ACh receptors?
They are believed to become desensitised through chronic coupling leading to withdrawal when nicotine is stopped
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What increases in activity?
target cells, particularly dopamine is thought to drive the rewarding effects of nicotine
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therefore how is dopamine released?
indirectly
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What is the withdrawal scale?
Anger, Anxiety, Cough and craving
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What is tobacco and anxiety?
amelioration of the withdrawal related aversive emotional state could be one reason why people continue smoking
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What is the N back task?
Press key when the word presented is the same as that presented 2 words ago
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What can be measured?
Sustained attention and working memory
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What can smokers had generally poorer cognitive performance?
consistent with pre existing cognitive deficit or toxicity of nicotine
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What is produced?
abstinence produced some cognitive impairment
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/What is the conclusion
Amelioration of withdrawal related cognitive deficit is one reason why people continue smoking
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What is the rapid visual information processing task?
series of numbers alternated in the centre of the screen, participants task was to press a key whenever a certain target sequence appeard
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What does the task demand/
Sustained vigilance, plus the maintenances of the memory for the target sequence
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What is the conclusion?
Smokers performed overall worse (shown as longer reaction times), nicotine enhanced performance although only smokers showed this effect at lower doses
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What is the NRT thought to do?
Stop withdrawal by maintaining ACh receptor occupancy
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What is Buproprion?
Thoguht to block the negative emotional state associated with wtihdrawal thereby protecting against relapse
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What is the 12 month sustained abstinence success rate?
2% with placebo and 5% with NRT or buproprion
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What were rats administered with?
Tobacco smoke and dopamine activity was measured by microelectrode placed in ventral tegmentum or substantia nigra
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What is Mecamylamine?
A nicotine receptor antagonist
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What is the mesolimbic dopamine pathway?
Thought to be critical for addiction
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What is the igostriatial responsible for?
(‘basal ganglia’); strongly implicated in motor control; loss of dopamine neurons here is a key neural marker for Parkinson’s disease
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What is the mesolimbic system responsible for?
ventral tegmental area (VTA, ‘tegmentum’) to the nucleus accumbens; thought to be the site of drug action and natural reward
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What is the mecocortical system for?
VTA (‘tegmentum’) to the cortex; role in negative symptoms of schizophrenia, flat affect, motivated and emotional behaviour, cognitive function
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What does nicotine do to the acetyl choline dopamine interactions?
induced excitation of the acetylcholine neurons is thought to excite mesolimbic dopamine (reward) cells via the branching pathway from the pedunculopontine nucleus
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What happened to rats with the electrical brain stimulation reward?
Unlike natural reward, such behaviour does not require deprivation (Panksepp & Trowill, 1967) Can displace other rewards, rats choosing BSR over food to the point of starvation (Routtenberg & Lindy, 1965)
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Wht happens to rats when they self administered nicotine directly into the VTA?
This nicotine self-administration could be abolished by antagonising activity at dopamine (SCH 23390) or ACh (DHBE) receptors
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What was the conclusion?
nicotine (via ACh receptors) increases activity in dopamine cells in the VTA; this increased activity mediates the addictive properties of nicotine
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electrical stimulation of dopamine pathways does not produce what?
A positive emotional facial reaction like pleasant foods, nor does it modify the positive facial reaction to pleasant foods
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What do humans undergoing electrical stimulation not report
experiencing pleasure, despite requesting that the stimulation continue • Suggests that dopamine does not mediate pleasure
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What does the distinction between wanting and liking show?
Addicts will often report wanting drugs, without experiencing much pleasure from them
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What is dopamine activity act as?
reinforcement signal strengthens the connection between drug-associated stimuli (e.g., the lever for a rat, or the smoking room for a human) and the drug seeking response (e.g., lever press, lighting a cigarette)
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As a result?
of this connection, drug associated stimuli come to elicit drug seeking behaviour
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What s the prediction of reinforcement model?
through associative learning, drug associated cues and contexts acquire the capacity to motivate drug seeking and taking behaviour
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Smokers who had just quite recorded what?
Almost 100% of lapses occurred when cigarettes were available and smoking was allowed • These data suggest situational cues for drug availability/ acceptability play a critical role in maintaining drug use
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What is the reinforcement model?
Through associative learning, drug associated cues and context acquire the capacity to motivate drug seeking and taking behaviour
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For example?
Pavolvian conditioning
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What is the habit theory?
Addict as a machine behaviour automatically controlled by external cues without any thought for consequence
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What do drugs reinforce?
dopamine activity reinforces the synaptic connection between drug cues and the drugseeking response that produced the drug
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As a consequence?
change in synaptic strength, drug cues elicit the drug seeking response directly
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what is the problem for the habit theory?
Craving,
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Why?
A mental image of the drug, incorporating its perceived appetitive value, its stimulus characteristics, circumstances under which it might be obtained, behaviours required to obtain the drug
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What do most addicts report?
drug seeking behaviour is undertaken intentionally, i.e. with a mental image of the drug driving their behaviour
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Therefore, the habit theory is what?
At odds with the apparent role of conscious decision making in the control of drug seeking behaviour
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What do studies of relationships between questionairre reports and actual smoking behaviour show?
If drug seeking was intentional, we’d expect a perfect correlation between craving and drug use behaviour; but meta analysis of studies to date suggests that the correlation is far from perfect
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Consequently what does this show?
addictive behaviour is sometimes intentional (i.e. controlled by a mental image or craving for the drug) and sometimes controlled automatically by external drug related cues just like other S-R habits
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What does this show on the cognitive model?
Drug users can switch between intentional and automatic modes of behavioural control
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What is the devaluation procedue?
demonstrate the transition from intentional control to behavioural autonomy with practice
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What are rats trained to do?
Press response for food pellets
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What hapens in a seperate environment?
given the oppurtunity to consume the food to satiation, reduce its value
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Then what happens?
Rats given the opportunity to press the food lever in extinction (no more food delivered)
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What did the rats show?
rats showed reduced lever pressing, indicating that this behaviour was controlled by a representation of the current value of the outcome of that behaviour (i.e. the rat has knowledge of the consequences of its behaviour)
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By contrast after extensive training what does this show?
rats became insensitive to devaluation, suggesting that behaviour had come under the control of a S-R habit (i.e. had become automatic)
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What does habit learning show?
Rats learned to press one lever for sucrose and one lever for alcohol then one of these rewards was devalued by pairing with lithium chloride to induce sickness
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What were the rats given the opportunity to press?
The two levers in extinction,
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Therefore?
If these two actions are now controlled by an expectation of the new low value of the rewards, then rats should reduce lever pressing • For whichever reward was devalued
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What happened when the lever pressed for sucrose was decreased?
Lever pressing for alcohol was not
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Conclusion?
after the same level of training, whereas food seeking was still controlled by an expectation of the consequences of the relevant behaviour, alcohol seeking had come under the control of a habit
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For alcohol what was the response?
external stimulus of the alcohol lever automatically, without engaging an expectation of the consequences of this behaviour
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What is the incentive salience theory?
Elaboration of habit theory - proposes that through Pavlovian conditioning, drug cues acquire the capacity to capture attention, which engages thought about the drug and drug use, which in turn causes drug users to initiate drug seeking/taking ..
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What shows attential bias for drug cues?
. Stroop task (e.g., Gross et al., 1993) 2. Interference with simple target detection (e.g., Sayette & Hufford, 1994) 3. Change detection (e.g., Jones et al., 2002) 4. Dot probe task (e.g., Ehrman et al., 2002) 5. Eye tracking (e.g., Rosse et al., 19
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What does the greater stroop effect become associated with?
Poorer treatment outcome in those addicted to drugs, such as: tobacco, alcohol, heroin and cocaine
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What is the expectancy theory?
Pavlovian stimuli only elicit CRs if they activate a representation or expectation of the outcome Evidence for both human conditioning in general (Lovibond & Shanks, 2002) and drug conditioning in particular
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What is SR habit learning?
: where drug cues automatically elicit drug seeking through the reinforcement of a S-R neural connection
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What is incentive salience?
where drug cues capture attention, which engages thoughts about drug use and which in turn motivates drug seeking
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What is goal directed learning?
where the drug cues engage a mental representation or expectation of the drug, which drives drug seeking behaviour
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What is SR habit learning?
: where drug cues automatically elicit drug seeking through the reinforcement of a S-R neural connection
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What is incentive salience?
where drug cues capture attention, which engages thoughts about drug use and which in turn motivates drug seeking
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What is goal directed learning?
where the drug cues engage a mental representation or expectation of the drug, which drives drug seeking behaviour
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Other cards in this set

Card 2

Front

What does Nicotine constitute?

Back

0.6-3% of dry weight of tobacco with biosynthesis taking place in the roots, accumulating in the leaves

Card 3

Front

How does Nicotine function?

Back

Preview of the front of card 3

Card 4

Front

Wha does an average cigarette yield?

Back

Preview of the front of card 4

Card 5

Front

What does the absorbtion of nicotine across lungs alveoli depend upon?

Back

Preview of the front of card 5
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