Nicotine Flashcards
About what percentage of dry tobacco weight is nicotine?
0.6-3%
What was nicotine first used as, and what was the problem with this?
A pesticide. However, people absorbed it through their skin and became ill.
The delivery system for nicotine is fast due to…
Attached tar molecules which make the acidity suitable for absorption across lung alveoli.
In inhalators, why does nicotine have to be at such a high dose?
Because there’s no tar, so less of it is absorbed.
What criteria does the DSM use to define nicotine dependence?
Tolerance, withdrawal, dose escalation, difficulty cutting down, reduce other activities, use despite problems.
About what percentage of current smokers meet the DSM criteria for dependence, according to Donny and Dierker (2007)?
60%
What are chippers?
Long term low-rate smokers (10% of smokers, according to Hyland (2005)).
At what age are people most likely to smoke?
18-25
What did Levin et al. (2003) find?
That adolescent rats self-administered more nicotine than adult rats.
Why might teenagers be more susceptible to nicotine addiction?
Perhaps the developing nervous system is particularly sensitive.
What does nicotine do to dopamine?
It’s an indirect dopamine agonist.
What did Gourlay and Benowitz (1997) find about the concentration of nicotine in arterial and venous blood?
It’s higher in arterial blood, which goes straight to the brain, meaning that it has a potent effect.
What pathways does nicotine primarily act on?
Cholinergic pathways - ACh.
Where are the major cholinergic projections?
The nucleus basalis and the peduculopontine nucleus (PPN) in the brainstem.
What are the functions of the nucleus basalis?
It regulates global functions in the cortex such as attention, arousal, motivation, memory and consciousness.
Where does the nucleus basalis project to?
The neocortex.
What is the role of the pedunculopontine nucleus in the brain?
It regulates level of arousal, motivation, and processing of incoming information.
Where does the PPN project to?
The thalamus.
How does nicotine interfere with acetylcholine transmission?
Nicotine has the correct molecular shape to act on ACh receptors - nicotinic cholinergic receptors.
What is ACh?
A neuromodulator.
What does ACh play an important role in?
Learning and intellectual function.
In what disease is there degeneration of the ACh system?
Alzheimer’s disease.
How are ACh receptors believed to become desensitised?
Through chronic coupling, leading to withdrawal when nicotine is stopped.
What is thought to drive the rewarding effects of nicotine?
Increased activity in the target cells, particularly dopamine.
What did Hughes et al (2007) find?
That smokers’ anxiety ratings increase when abstaining - withdrawal related aversive state, could be why people continue smoking.
What did Jacobsen et al (2005) do?
Used the ‘N-back’ task (press key when word is same as 2 previously) to measure sustained attention and working memory in smokers and non-smokers when smoking or abstinent.
What did Jacobsen et al (2005) find?
That smokers had generally poorer cognitive performance and abstinence produced some cognitive impairment (perhaps a reason why some people continue to smoke).
What did Foulds et al (1996) do?
Used a rapid visual information processing task (recognising a number sequence, requires memory and vigilance) to test nicotine-induced reduction of reaction time - injected smoker and non-smokers with nicotine.
What did Foulds et al (1996) find?
That nicotine reduced latencies in smokers, but only the higher dose affected non-smokers. Smokers performed worse overall.
How is nicotine replacement therapy thought to stop withdrawal?
It maintains ACh receptor occupancy. However, has the problem of dependence.
What is bupropin?
An anti-depressant used to help smokers quit.
How is buproprion thought to prevent relapse?
By blocking the negative emotional state associated with withdrawal.
According to Wang (2008) and Wu (2006), what are the 12-month sustained abstinence rates?
2% for a placebo, 5% for NRT and buproprion.
What did Fà et al (2000) do?
Connected rats to an artificial respirator through which tobacco smoke (containing nicotine) could be delivered for two minutes during each trial. Measured brain activity in the VTA/substantia nigra.
Later injected with mecamylamine (nicotine receptor antagonist).
What did Fà et al (2000) find?
Tobacco smoke caused a significant increase in VTA neuronal firing, and a smaller effect in the substantia nigra. Mecamylamine blocked the effect of the smoke, suggesting that the effect is mediated by nicotinic cholinergic neurons.
What dopamine pathway is believed to be critical for addiction?
The mesolimbic pathway, between the VTA and nucleus accumbens.
Nicotine (via ACh receptors) increases DA activity in the VTA which mediates the addictive properties of nicotine.
What is another name for the VTA?
The tegmentum.
How does nicotine’s effect on ACh interact with its effect on dopamine?
Nicotine-induced excitation of ACh neurons is thought to excite mesolimbic dopamine cells via the branching pathway from the PPN.
In what way is electrical stimulation of the mesolimbic dopamine pathway different to natural rewards, according to Panksepp and Trowill (1967)?
It doesn’t require deprivation.
What evidence do Routtenberg and Lindy (1965) give for the fact that electrical stimulation of the mesolimbic dopamine pathway can displace other rewards?
Rats choose ESB over food to the point of starvation.
What did David (2006) find?
That when rats self-administered nicotine into the VTA, it could be abolished by antagonising activity at dopamine (SCH 23390) or ACh (DHBE) receptors.
What does electrical stimulation of dopamine pathways not produce?
A positive emotional facial reaction.
What do humans undergoing electrical stimulation of dopamine pathways experience?
Appparently, no pleasure, but they request that it continue.
What distinction did Robinson and Berridge (1993) make?
The difference between wanting and liking - addicts often report wanting drugs without experiencing pleasure from them.
How is it suggested that dopamine is involved in reinforcement of addictive behaviours?
Dopamine activity as a reinforcement signal strengthens the connection between drug-associated stimuli and the drug-seeking response. Consequently, drug-associated stimuli become able to elicit drug-seeking behaviour (CC).
What did Schiffman (1996) find?
Smokers who’ve just quit are most likely to lapse when cigarettes are available and smoking allowed (almost 100% of recorded lapses).
What do Schiffman (1996)’s findings suggest?
That situational cues for drug availability/acceptability play a critical role in maintaining drug use - classical conditioning.
What does habit theory envisage the addict as?
An automaton whose behaviour is controlled by external cues.
According to habit theory, what does drug-induced dopamine do?
It reinforces the synpatic connection between drug cues and drug-seeking response. Therefore drug cues elicit the drug-seeking response directly.
In what way does craving represent a problem for habit theory?
Craving, seeing an image of the drug and intentionally deciding to give in, is a problem because habit theory doesn’t account for conscious decision making as a factor in the control of drug seeking behaviour.
What does Tiffany (1990)’s cognitive model of drug use suggest?
Drug seeking is partially intentional (otherwise there would be a perfect correlation between craving and drug use behaviour) and partly unintentional - due to external cues.
Thus, drug users can switch between intentional and automatic modes of behavioural control.
What is devaluation?
The idea that behaviour is controlled by a representation of the current value of the behaviour’s outcome.
How did Dickinson (1985) support devaluation theory?
Devaluation procedure:
- Trained rats to press lever for food
- In a separate environment given plenty of food (reduce value)
- Rats given opportunity to press lever in extinction.
Most rats showed devaluation - reduced lever pressing, but not extensively trained lever-pressing rats; they were insensitive to devaluation = automatic behaviour.
What did Dickinson (2002) find?
That habit learning is quicker for drugs than natural rewards - in a devaluation procedure lever pressing for sucrose was decreased but lever pressing for alcohol was not, after the same level of training. Alcohol seeking behaviour had come under the control of a habit and was unaffected by expectations.
What is incentive salience theory?
An elaboration of habit theory - proposes that through CC drug cues require the capacity to capture attention, engaging thought about the drug and drug use, leading to drug seeking behaviour.
What types of studies can show attentional bias for drug cues?
- (Emotional) Stroop task (Gross et al, 1993)
- Interference with simple target detection (Sayette and Hufford, 1994)
- Change detection (Jones et al, 2002)
- Dot probe task (Ehrman et al, 2002)
- Eye tracking (Rosse et al, 1993)
What is greater Stroop attentional bias associated with?
Poorer treatment outcome in addicts.
Emotional Stroop tasks on various drug addictions have been conducted. By who, and with what drugs?
- Waters (2003) - tobacco
- Cox (2002, 2007) - alcohol
- Marissen (2006) - heroin
- Carpenter (2006) - cocaine
Who verified expectancy theory (goal-directed learning)?
Generally - Lovibond and Shanks (2002)
Drug conditioning - Hogarth (2006)
What did Hogarth et al (2006) do?
Used a game with four images where pts played for cigarettes (aware and unaware conditions) to demonstrate that stimuli only elicit conditioned responses if they elicit a representation of the outcome.
In what three ways do drug cues motivate drug seeking?
- Stimulus-response habit learning
- Incentive salience
- Goal-directed learning.
What is expectancy theory?
The idea that it is axiomatic that conditioned stimuli only produce the response if they elicit an expectation of the outcome.
