Nicotine

Question 1

Alzheimer’s disease, what neurons die first?

Answer 1

cholinergic neurons in the basal forebrain die first.

Question 2

Schizophrenia, Parkinson’s Disease, and Alzheimer’s disease – what is known to reduce symptoms?

Answer 2

cholinergic agonists (nicotine is one example) reduce symptoms.

Question 3

Pharmacokinetics of Nicotine

Answer 3

usually ingested by inhalation or orally.

Question 4

Absorption of tobacco

Answer 4

absorption depends on type of tobacco but it is generally well-absorbed orally and from small intestine, and skin; both fat and water soluble; significant levels in the brain w/in 1 min (inhaled and peak levels w/in 10 min (inhaled) to 30 min (oral chew)

Question 5

ED50 of tobacco

Answer 5

about .5mg – 1 mg (cigarette contains about 8 mg total)

Question 6

Distribution in body of nicotine

Answer 6

rapid distribution throughout body, with highest concentrations in brain, liver, and lungs

Question 7

Where is nicotine metabolized?

Answer 7

90% metabolized in liver by cytochrome P450 2A6 before it is eliminated in urine; in a ½ life of 2 hr

Question 8

How does tolerance develop to nicotine?

Answer 8

Tolerance develops due to activation of hepatic enzymes

Question 9

LD 50 of nicotine

Answer 9

60 mg (10 cigarettes, if all nicotine absorbed); thus TI ~60 to 100

Question 10

How does nicotine arouse the CNS?

Answer 10

Nicotinic activation in cortex gives a feeling of arousal (more attentive) – likely due to nACh activation of the LC/brainstem neurons involved in sleep/wake and arousal; and in activation of cortical/thalamic neurons.

Question 11

How does nicotine produce reward in the CNS?

Answer 11

due to stimulation of mesolimbic DA neurons

Question 12

How and where does nicotine produce relaxation?

Answer 12

due in part to decreased sensory feedback from muscles, due to decreased contractions of muscles caused by nicotine (happens in the PNS)

Nicotine can help one relax by paralysis of pulmonary tissue

Question 13

How does nicotine act as an agonist? antagonist?

Answer 13

Nicotine is an agonist when there is low activation of nicotinic acetylcholine receptors – later it can act as an antagonist (when it is desensitizes the nAChR)

Question 14

At LD50, what happens with cigarettes?

Answer 14

The muscles in your lungs get suppressed to the point where you stop breathing.

Question 15

How does nicotine affect the brain?

Answer 15

Very potent effect on cortical and hippocampal neurons… increases cortical activity (eg. Increased reactions; increased attention and concentration; enhanced cognitive function)

Question 16

Subsensitive

Answer 16

the receptor is there, change in flutter frequency, it flutters at a slower rate.

Question 17

Locus coeruleus neurons fire on their own, they are said to be ___________

Answer 17

Locus coeruleus neurons fire on their own, they are said to be spontaneously active.

Question 18

Norepinephrine, ionotropic or metabotropic?

Answer 18

always works through second messengers.

Question 19

how does the locus coeruleus relate to inhibition/excitation?

Answer 19

Normally we’re biased towards inhibition, however, when the LC is activated, there is a higher bias toward excitation.