Nicotine Addiction Flashcards

Question

nAChRs with repeated smoking (3)

Answer 1

B/w cigarettes nAChRs are mainly desensitised (acute tolerance) Next cigarette activates a small pool of receptors that are still responsive, producing pleasurable effects In chronic smokers (e.g. with daily smoking for 6 months or longer): – Tolerance – Withdrawal syndrome on cessation of smoking – Long-term desensitisation of nAChRs – Increase in receptor density (upreg. of nAChRs) as a compensatory response to desensitisation of the large proportion the total no. of nAChRs receptors

Answer 2

rat brain treated w/saline (smokers = darker) Upreg.of nAChRs as a compensatory response to desensitisation of nAChRs increase in r's associated w/craving + dependence

Answer 3

either 1) incr. protein synth = transc. +translat = not here X or 2)interfere w/reg. of r's: nicotine inc. internalised r's in vesicles to go to membrane to be used

Answer 4

Autopsy studies comparing smokers to nonsmokers reveal up to 400% increases in brain nicotine receptors Reversibility extent, time course, and variability is unclear

Answer 5

* Initial activation causes pleasure response but... * Dopamine falls quickly over next 2hrs * As levels fall the smoker feels displeasure/withdrawal * The next cigarette reduces cravings and other withdrawal symptoms + produces some +ve effects * This reinforces the compulsion to smoke * Environmental cues are also important in producing addiction

Answer 6

* Each cigarette delivers 1.2-2.9mg of nicotine * A typical pack-a-day smoker absorbs 20-40mg of nicotine/day * Half-life is ~ 2hours * During a typical day, nicotine accumulates over 6-8 hours (3-4 half-lives) * The increment is 5-30ng/ml after each cigarette (depending on how the cigarette is smoked) * More frequent smoking reduces fluctuations in nicotine plasma concentration * The plateau (10-50ng/ml) is usually reached in the early afternoon

Answer 7

graph w/ uneven bell shaped curve - jagged lines throuugh grey shape = fluctuatiosn of nicotine (DA) - bottom solid line - threshold below which = withdrawal - top solid line - threshold above which you get pleasurable effects - grey shape = feeling neutral - neighter pleasure or withdrawal

Answer 8

* Tobacco users maintain a minimum serum nicotine concentration in order to – Prevent withdrawal symptoms – Maintain pleasure/arousal – Modulate mood * Users self-titrate nicotine intake by: – Smoking/dipping more frequently – Smoking more intensely – Obstructing vents on low-nicotine brand cigarettes

Answer 9

* Nicotine plasma concentration significantly drops overnight, which leads to withdrawal symptoms in the morning in chronic smokers. * Withdrawal onset is usually within a few hours after last cigarette * Nicotine withdrawal syndrome includes: Mood changes * 1st morning cigarette produces the most pleasurable effect – After an overnight abstinence more receptors become available for activation – It also relieves withdrawal symptoms * The earlier the smoker begins to smoke after waking in the morning the more severe the dependence * If abstinence continues, withdrawal symptoms peak at 24-48hrs and gradually subside over several weeks.

Answer 10

- dysphoria, depressive mood – Irritability, frustration or anger – Anxiety, restlessness – Difficulty concentrating, impaired attention – Hunger, increased appetite or weight gain – Craving * Some symptoms persist for months – mild depression, dysphoria and anhedonia

Answer 11

Environment  Tobacco advertising  Conditioned stimuli  Social interactions Physiology  Genetic predisposition  Coexisting medical conditions Pharmacology  Alleviation of withdrawal symptoms  Weight control  Pleasure

Answer 12

Some places, times and situations are closely associated w/smoking and enhance craving: – Morning coffee with breakfast – Coffee shop – Tea breaks

Answer 13

* Heritability ~50% (range 28-84%) * Effect of gene polymorphisms: – People with defective alleles of CYP2A6 gene= slow metabol. of nicotine and lower rates of smoking + tobacco dependence. – People with CHRNA4 gene polymorphism (gene coding for α4 subunit of the nicotinic Ach receptor) have higher rates of tobacco dependence

Answer 14

polymorph of alpha5 - inc. chances of nicotine addiction + lung cancer ko mice - with self-amin test  Nicotine intake has bell-shaped conc curve - at a higher conc = aversion  Up-phase represents rewarding component, unaffected by deletion of alpha5  Down phase reflects the aversive effects of higher doses of nicotine, significantly greater responses in a5 KO reintroduced alpha5 construct in diff parts of brain - expected results, until introduced in medial habenula =Identification of novel pathway that transmits inhibitory motivational signal which limits nicotine intake (opposes mesoaccubens reward)

Answer 15

People with psychiatric disorders and substance use disorders have 2-4x higher rates of smoking (range 41% and 67% respectively) than the general population * 40-88% of patients with schizophrenia smoke * Higher rates of depression in smokers * Higher rate of smoking in substance abusers

Answer 16

* Possibly reduces symptom severity in schizophrenia (self-medication hypothesis) – There is deficient endogenous central nicotinic neurotrans in schizophrenia = causes a disruption of sensory gating (a possible mechanism for delusions) – Exogenous nicotine partly compensates for this deficiency. – Schizophrenic patients smoke larger amounts of cigarettes per day and extract more nicotine from them – sig. health risk. – Therapeutic use of safe forms of nicotine in schizophrenia has been proposed. * Reduces risk of Parkinson’s disease – Lower incidence of PD in smokers – Benefit correlates with the intensity and duration of smoking. – Does not appear to be due to publication bias – Nicotine neuroprotective for nigrostriatal neurons * Does it reduce prevalence of Alzheimer’s disease? – After controlling for tobacco industry affiliation, smoking has been found to increase the risk of Alzheimer’s disease,

Answer 17

Tobacco Dependence: Treatment should address the physiological and the behavioural aspects of dependence Physiological: The addiction to nicotine -Treatment =Medications for cessation Behavioural: The habit of using tobacco- Treatment =Behaviour change program

Nicotine Addiction Flashcards

(41 cards)