nicotine

Question 1

what were cigarette advertisements previously like?

Answer 1

promoted cigarettes as produced aimed to help soldiers cope with the stresses of war

Question 2

what is cigarette packaging now?

Answer 2

awareness of health hazards

introducing barriers to access to younger people (minimum of 20 cigarettes)

unappealing

increased duty

Question 3

what is the health and economic impact?

Answer 3

smoking is a health hazard and leading cause of premature death - lung cancer, increased risk of stroke and cardiovascular diseases

UK government spends up to £17* billion per year on treating tobacco-related illness and promoting abstinence/prevention

Question 4

what is tobacco?

Answer 4

tobacco cultivation requires mild, sunny climates

nicotine biosynthesis takes place in the roots of tobacco plant and accumulates in the leaves

nicotine is an insect-targeting neurotoxin and was used an insecticide

nicotine constitutes around 0.63% of drug weight of tobacco

Question 5

what are the top producers of tobacco?

Answer 5

China

India

Indonesia

Zimbabwe

Brazil

Question 6

what is the pharmacology of nicotine?

Answer 6

cigarette contains 6-11mg of nicotine but only 1-3mg absorbed

nicotine attaches to tar molecules of cigarette smoke

tar is acidic and makes conditions more suitable for nicotine absorption across lung alveoli into blood stream

absorption profile is fast and spiked (within minutes)

arterial nicotine rose more rapidly and reached higher peak relative to venous blood suggesting that nicotine is rapidly delivered to target sites in CNS

fast “hit” leads to stronger reinforcement, a key factor in habit formation and substance dependence

pure nicotine in inhalators (with no tar) has to be at an extremely high dose to achieve the same level of absorption as a cigarette

Question 7

what is arterial nicotine?

Answer 7

travelling away from the heart and lungs

Question 8

what is the difference between inhaled nicotine and oral forms?

Answer 8

inhaled nicotine reaches brain much faster due to rapid lung absorption and direct arterial transport

Question 9

what has been a significant hurdle for the nicotine replacement industry?

Answer 9

difficulty in replicating the fast, spiked absorption profile of cigarettes

Question 10

what are the neural mechanisms of nicotine?

Answer 10

nicotine is an agonist at nicotinic ACh receptors (nAChRs)

ACh is a “neuromodulator” which can influence activity in target cells

ACh plays an important role in learning and intellectual function - degeneration in this system is seen in Alzheimer’s disease

Question 11

what does nicotine do to ACh neurons?

Answer 11

activates ACh neurons in pedunculopontine nucleus (PPT)

these neurons excite DA-producing cells in the VTA - occurs indirectly via a branching pathway

as a result, nicotine increases DA release in the mesolimbic pathway - specifically from VTA to NAc

this dopamine surge is believed to play a central role in the development of addiction

Question 12

What was Fa et al’s (2000) study into DA activity in the VTA?

Answer 12

rats were administered tobacco smoke

DA activity was measured by microelectrode placed in VTA

increased activity observed following tobacco administration

but reduced with administration of nAChRs antagonist - mecamylamine

Question 13

what is brain stimulation reward?

Answer 13

rats learn to press a lever to obtain electrical brain stimulation reward of the mesolimbic dopamine pathway

unlike natural reward, such behaviour does not require deprivation (Panksepp and Trowill, 1967)

can displace other rewards, rats choosing stimulation reward over food to the point of starvation (Routtenberg and Lindy, 1965)

Question 14

what was found through nicotine self-administration studies?

Answer 14

rats self-administered nicotine directly into VTA, indicating nicotine has rewarding effects

blocking DA receptors (SCH 23390) stopped self-administration, suggesting nicotine’s effects depend on DA

conclusion - nicotine stimulates ACh receptors, increases DA activity in VTA, increased activity mediates the addictive properties of nicotine

blocking ACh receptors (using DHBE) also stopped self-administration so nicotine acts through ACh receptors

Question 15

what is it suggested DA activity in the ventral striatum does?

Answer 15

increased activity in the target cells, particularly dopamine, is thought to drive the rewarding/reinforcing effects of nicotine

Question 16

what are susceptibility factors?

Answer 16

nicotine metabolism

adolescents

Question 17

how is nicotine metabolism a susceptibility factor?

Answer 17

differences in nicotine metabolism due to genetic variations may account for differences in susceptibility across individuals

slower metabolisers of nicotine need to smoke fewer cigarettes per day, thus reduces the likelihood of them becoming dependent

Question 18

how is adolescence a susceptibility factor?

Answer 18

age of first exposure

tobacco usage is higher in smokers adopting the habit earlier (18-25 years) rather than later (over 26 years of age)

Question 19

what was the study into smoking in adolescent rats?

Answer 19

rats given the opportunity to self-administer (lever press for) nicotine

adolescent rats worked harder for nicotine and took a larger amount of nicotine than adults (Levin et al, 2003)

conclusions - adolescents more vulnerable to nicotine addiction

Question 20

what is clinical dependence?

Answer 20

diagnostic and statistical manual of mental health disorders (DSM)

tolerance - find that you had to use much more tobacco that you once did to get the effect you want?

withdrawal - often use tobacco just after getting up or shortly after getting up in the morning?

escalation of dose - have a period when you often used tobacco more than you intended to?

difficulty cutting down - more than once wanted to stop or cut down on your tobacco use?

reduce other activities - give up or cut down on activities that you were interested in or that gave you pleasure because tobacco use was not permitted at the activity?

use despite problems - continue to use tobacco even though you knew it was causing you a health problem or making a health problem worse?

Question 21

what is nicotine dependence?

Answer 21

high proportion of users become dependent - 60% of current smokers meet the DSM criteria for nicotine dependence (Donny and Dierker, 2007)

not all smokers become dependent - at least 10% of current smokers are long-term low-rate smokers (Hyland, 2005)

tobacco dependence is not the inevitable consequence of exposure to tobacco

interaction between exposure and initial vulnerability

Question 22

what are the withdrawal effects?

Answer 22

ACh receptors become desensitised through chronic coupling after prolonger exposure

leads to withdrawal effects when nicotine stopped

urges and cravings, irritated, anxious, restlessness, concentration difficulties, sleeping difficulties

smokers adjust their cigarette use to maintain nicotine levels sufficient to avoid withdrawal effects

Question 23

when do lapses happen?

Answer 23

long term smoking cessation is challenging

smokers who had just quit recorded the situations in which they lapsed in diary studies

almost 100% of lapses occurred when cigarettes were available and smoking was allowed

this data suggest situational cues for drug availability/acceptability play a critical role in maintaining drug use

Question 24

what is Nicotine Replacement Therapy (NRT)

Answer 24

provides nicotine in an alternative form, helps reduce cravings and withdrawal effects, making it easier to quit smoking

alleviate withdrawal symptoms by maintaining ACh receptor occupancy

however it may lead to transfer of dependence rather than completely eliminating nicotine addiction

Question 25

what is Bupropion?

Answer 25

antidepressant marketed as Zyban thought to reduce negative emotional effects of withdrawal helping to prevent relapse works by inhibiting reuptake of DA and NA

Question 26

what is 12-month sustained abstinence success rate?

Answer 26

relatively low approximately 2% of individuals achieving long-term abstinence using a placebo success rate increases to about 5% for those using either NRT or bupropion (Wang, 2008; Wu, 2006)

Question 27

how can exposure models be tested?

Answer 27

nicotine offers convenient way to study substance addiction legal drug that is widely available can be administered in pure form as a tablet, vapour, etc

Question 28

what are habit-based accounts?

Answer 28

behaviour becomes automatic, triggered by cues, insensitive to outcomes Stimulus-Response (S-R) theory incentive salience theory, attentional bias outcome devaluation studies

Question 29

what is the stimulus-response habit?

Answer 29

reinforcement model - through associative learning, drug associated cues and contexts acquire the capacity to motivate drug seeking and taking behaviour Pavlovian conditioning addict as a machine - behaviour automatically controlled by external cues without any thought for the consequences drug-induced DA activity reinforces the synaptic connection between drug cues and the drug-seeking response that produced the drug as a consequence of this change in synaptic strength, drug cues elicit the drug seeking response directly

Question 30

what is the procedure of outcome devaluation study?

Answer 30

phase 1 - instrumental training - rats trained to press a lever to receive food pellets, establishes a goal-directed action-outcome association phase 2 - outcome devaluation - in a different environments, rats are given free access to the same food until they are satiated, reducing the current values of the food outcome phase 3 - extinction test - rats are placed back in the original context and allowed to press the lever but no food delivered, measures whether level pressing persists despite devaluation

Question 31

what is the extinction test interpretation of an outcome devaluation study?

Answer 31

if responding decrease - behaviour goal directed, controlled by an outcome representation, animals adjust their action based on the current value of the outcomes if responding persists, behaviour has become habitual, controlled by S-R associations, responding is insensitive to changes in outcome value

Question 32

what was Dickinson's (1985) outcome devaluation study?

Answer 32

rats trained to press one lever for sucrose, one for alcohol one reward devalued via lithium chloride (induced sickness) rats then tested in extinction (no reward delivered) if behaviour goal directed then rats should press less for the devalued reward but if the behaviour is habitual, rats will continue pressing despite devaluation sucrose level - pressing decreased - behaviour goal-directed alcohol lever - pressing unchanged - behaviour habitual food-seeking involved an expectation of outcome valye alcohol-seeking was stimulus driven - automatic, insensitive to consequences suggests alcohol-seeking behaviour (and by extension other addictive behaviours) may become habitual more quickly

Question 33

what is the incentive salience theory?

Answer 33

elaboration of habit theory (Robinson and Berridge, 2003) - proposes that drug cues acquire the capacity to capture attention (through Pavlovian conditioning) - attentional bias attention results in engagement of thoughts about the drug and drug use which in turn causes drug users to initiate drug seeking/taking addiction is driven not just by pleasure but by intense motivation to seek drug - even when pleasure fades over time, drug-related cues become sensitised and trigger strong "wanting" even if "liking" is reduced explains why people continue to seek drugs despite no longer enjoying them - hallmark of compulsive use

Question 34

how has attentional bias been shown in those with drug dependency?

Answer 34

simple target detection (Sayette and Hufford, 1994) and change tasks (Jones et al, 2002) are easier for those with drug dependency if image relates to drug use eye tracking (Rosse et al, 1993) - eye-gaze drawn more easily to drug related cues Stroop task (Gross et al, 1993) - those with drug dependency are slower to name the colour of drug-related words greater Stroop attentional bias is associated with poorer treatment outcome in those addicted to various drugs (tobacco, alcohol, heroin, cocaine)

Question 35

what is habit theory at odds with?

Answer 35

apparent role of conscious (albeit compulsive) decision making in the control of drug seeking behaviour an urge or craving to smoke often accompanied relapse and drug use

Question 36

what are goal-directed accounts?

Answer 36

behaviour is deliberate, based on expected value of outcomes mental image of how pleasurable/rewarding something will be cravings expectancy theory

Question 37

how do cravings relate to goal-directed accounts?

Answer 37

most addicts report that their drug seeking behaviour is undertaken intentionally (i.e. with mental image of the drug driving their behaviour) a mental image of the drug, incorporating its perceived appetitive value, its stimulus characteristics, circumstances under which it might be obtained, behaviour required to obtain the drug

Question 38

what is the expectancy theory?

Answer 38

proposes that behaviour is goal-directed, driven by learned beliefs about outcomes Pavlovian stimuli (e.g. cues and signals) only elicit a conditioned response when they activate a mental representation of the expected outcomes evidence in general human conditioning (Lovibond and Shanks, 2002) drug conditioning (Hogarth et al, 2006) - demonstrated that expectancy awareness predicts drug-seeking behaviour

Question 39

what was Hogarth et al's (2006) study into the expectancy theory?

Answer 39

conditioning schedule - A = predicts reward, B = predicts no reward trial structure - discriminative stimuli presented in compounds pairs, expectancy rating (E) = "how likely are you to win?", response (R) = choose to seek or not to seek drug, outcome (O) = win or lose 1/4 of a cigarette smokers divided into two groups based on their awareness of stimulus-outcome contingencies aware group - participants who recognised the association between specific cues and outcomes unaware group - participants who did not recognise these associations higher expectancy rating and seeking response for positive stimuli (A) but only in aware group clear difference in expectancy following A vs B in the aware but not the unaware group expectancy plays a role in substance seeking behaviour

Question 40

what cognitive models?

Answer 40

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 correlation is far from perfect

Question 41

what did Tiffany (1990) suggest?

Answer 41

proposed that drug users can switch between intentional and automatic modes of behavioural control sometimes intentional (i.e. controlled by a mental image or craving for the drug) sometimes controlled automatically by external drug related cues just like other S-R habits