Tobacco

Question 1

3 Treatments for Nicotine Dependence (3)

Answer 1

Nicotine Replacement Therapy

Bupropion

Varenicline (Champix)

Question 2

Nicotine Replacement Therapy (2)

Answer 2

relieves psychological and physiological effects of withdrawal

no abstinence from nicotine

Question 3

What is the effect of Bupropion (4)

Answer 3

blocks monoamine uptake

nicotinic antagonist

antidepressant by increase NA in accumbens

can induce eating disorders, mania (bipolar) and seizures

Question 4

What are the effects of Varenicline and what is the commercial name (3)

Answer 4

partial a4B2 AchR agonist, full a7 agonist

more effective than NRT

Champix

Question 5

Nicotine mimics acetylcholine in the brain, in which area of the brain is the highest density of Ach neurons? (1)

Answer 5

Striatum

Question 6

How do nAchR’s modulate neurotransmission in the mammalian brain? (2)

Answer 6

influence excitability on post synpatic cells

modulate NT release at presynaptic sites

Question 7

Explain paradoxical upregulation of nAchR (1)

Answer 7

there is an increase in binding sites in brains of smokers and mice that are exposed to chronic nicotine

Question 8

What form of nAchR is most important with regards to nicotine dependence, what is the evidence? (4)

Answer 8

a4B2

nicotine doesnt activate VTA neurons B2 KO mice

nicotine does not promote DA release

B2 KO mice dont self administer

Question 9

Explain the mechanism of Champix (4)

Answer 9

partial agonist of a4B2

mimics nicotine to avoid withdrawal but it in itself isnt rewarding

prevents nicotine from producing a further effect

1 yr quit rates are 20% similiar to NRT

Question 10

Of the 3 subunit varieties of nAchR’s, which one has the highest nicotine sensitivity and which has the highest calcium permeability? (2)

(a4) 2(B2)3
(a4) 3(B2)2
(a4) 2(B2)2(a5)1

Answer 10

(a4)2(B2)3 has highest nicotine sensitivity

(a4) 3(B2)2
(a4) 2(B2)2(a5)1 have equally high calcium permeability

Question 11

Explain the increased nicotine intake in a5 KO mice (6)

Answer 11

up phase of bell curve is rewarding component unaffected by a5

down phase of bell curve is aversive effects of higher doses, this is greatly increased by a5 KO mice

‘rescue’ of a5 nAchRs in the habenulo-interpeduncular tract normalises nicotine intake

this enhances NMDA receptor mediated glutamergic transmission in IPN

nicotine induced IPN activity relays an inhibitory motivational signal that limits further drug intake

deficient a5 nAchR signalling diminishes the magnitude of the inhibitory motivational signal, permitting larger amount of nicotine to be consumed