Nicotine

Question 1

How is nicotine cultivated?

Answer 1

dried tobacco leaves contain ~6% nicotine (active alkaloid)

Question 2

What is in tobacco smoke?

Answer 2

nicotine, carbon monoxide and thousands of particulates (many are carcinogenic)

Question 3

What are the risks of smoking?

Answer 3

around 1/4 cancer deaths not caused by genetic factors are attributable to smoking tobacco
half of all lifetime smokers die prematurely because of cigarette-induced disease

Question 4

What factors can influence smoking?

Answer 4

socioeconomic; bachelor degree holders are less likely to smoke
age; highest level of smoking 20-34
men smoke more than women
price
culture

Question 5

Routes of administration

Answer 5

most routes are effective except for ingestion

smoking, snuff, gum, chewing tobacco

Question 6

Which is the optimal route of administration for peak subjective high?

Answer 6

inhaling cigarette smoke allows nicotine to reach the brain in ~ 7 seconds

Question 7

When can nicotine be poisonous?

Answer 7

~60mg is a lethal dose in humans

each cigarette contains ~6-11mg, of which 1-3mg is absorbed

Question 8

What aversive symptoms can high nicotine doses cause?

Answer 8

nausea, dizziness, sweating, heart racing, stomach ache; potent activator of the sympathetic and parasympathetic nervous system

Question 9

How can nicotine be lethal?

Answer 9

very high dose can cause a depolarisation block on the muscles involved in respiration

Question 10

How is nicotine metabolised?

Answer 10

nicotine is metabolised into cotinine by the cytochrome P450 2A6 enzyme and excreted through urine
evidence; methoxsalen inhibits enzyme and creates unpleasant symptoms at lower concs

Question 11

What are the subjective effects of nicotine?

Answer 11

relaxation
stress alleviation
concentration; sustained attention and memory

Question 12

How can nicotine self-administration be modelled in rodents?

Answer 12

IV nicotine SA can be difficult to achieve
behaviour is strongly controlled by conditioned cues
- e.g. humans; smoke, rodents; light/sound etc.
conditioned cues are strong at low doses but not at high doses

Question 13

What metabolic changes are associated with smoking?

Answer 13

reduction in monoamine oxidase B

Question 14

What is the function of monoamine oxidases?

Answer 14

break down monoamine NT’s (DA and NE) into inactive metabolites

Question 15

What are the implications of reduced MAO?

Answer 15

psychiatric disorders

lower rates of Parkinsons Disease

Question 16

What evidence is there for the role of MAO in nicotine SA?

Answer 16

MAO inhibitors greatly facilitate nicotine SA and sensitisation
extended access + MAO inhibition = greatest escalation of nicotine SA

Question 17

What are the withdrawal symptoms of nicotine addiction?

Answer 17

irritability, anxiety, difficulty concentrating
disappear after 4 weeks
nicotine replacement therapy can help

Question 18

Where is acetylcholine found?

Answer 18

the neuromuscular junction

Question 19

How is ACh synthesised?

Answer 19

choline (dietary precursor) + acetyl coenzyme A + choline acetyltransferase = acetylcholine + coenzyme A

Question 20

How is ACh degraded?

Answer 20

Ahh + acetylcholinesterase = choline + acetic acid

Question 21

What are the classes of ACh receptor?

Answer 21

metabotropic; muscarinic

ionotropic; nicotinic

Question 22

What is the structure of nAChR?

Answer 22

pentameric ligand-gated cation channel

alpha and beta subunits (12 types) can combine in various ways

Question 23

What is the structure of nAChR?

Answer 23

pentameric ligand-gated cation channel

alpha and beta subunits (12 types) can combine in various ways; usually 3a and 2b

Question 24

What is the structure of mAChR?

Answer 24

g-protein coupled receptor that serves various functions in the CNS

Question 25

How do ACh receptors work?

Answer 25

to pass cations and allow rapid depolarisation (EPSPs)

Question 26

What are the peripheral actions of AChRs?

Answer 26

autonomic nervous system to regulate physiological functions

• sympathetic; HR, BP, NE and E secretion from adrenal glands
• parasympathetic; stomach acid and intestinal motility

Question 27

What are the main neurological actions of nicotine?

Answer 27

increased VTA firing and accumbens dopamine release

accumbal dopamine is required for nicotine SA

Question 28

Which ACh receptor is implicated in nicotine SA?

Answer 28

beta2 K/O mice do not show VTA firing in response to nicotine; b2 nAChR implicated in reinforcing effects of nicotine in VTA