BG II

Question 1

Chronic nicotine use increases the density of which receptors in the prefrontal cortex? Is this due to transcriptional upregulation?

Answer 1

• heteromeric a4b2 nicotinic receptors

- No! due to DEC degradation + increased assembly, NOT due to upregulation of transcription.

Question 2

While with chronic nicotine use we see inc in a4b2 nicotinic receptors in the prefrontal cortex, with ___, __, and ___ we see DECREASE, so maybe …

Answer 2

• aging, dementia, and Alzheimer’s

- Upregulation of heteromeric a4b2 nicotinic receptor enhances cognition and attention

Question 3

Alcohol has a ___(low/high) affinity interactions with biomolecules, need ___ (lower/higher) concentrations of alcohol to bind to receptors, compared to other drugs.

Answer 3

low affinity

higher concentration

Question 4

Properties of Alcohol

Answer 4

• Amphipathic, passes through cell membrane.
• CNS depressant
• anxiolytic (relieves anxiety), hypnotic (sleepy), anesthetic

Question 5

Alcohol’s mechanism of action on the CNS

Answer 5

• Inhibition of excitatory neurotransmission
• Enhances inhibitory neurotransmissions
• Modulates dopamine release within ventral striatum
• Disturbs balance of neurotransmissions, leading to disinhibiton, ataxia and sedation
• Repeated use = tolerance

Question 6

does alcohol enhance or inhibit these receptors?

• NMDA
• cys loop
• 5HT

Answer 6

• inhibition of current through NMDA channels (needed for LTP)
• enhances current through Cys loop ligand gated ion channels (GABA-A and nAChR, like alpha7)
• potentiates 5-HT3 receptor (selective cationic ch)

Question 7

Alcohol inhibits ligand action for these 3 receptors:

Answer 7

NMDA receptor
Kainate receptor
Voltage-sensitive Ca2+ channels

Question 8

Examples of schedule I drugs

Answer 8

Heroin 
LSD
Tetrahydrogestrinone (THG) 
MDMA “ecstasy”
Cannabis

Question 9

with CHRONIC use, which one causes sensitization – alcohol or cocaine?

Answer 9

alcohol = tolerance
cocaine = sensitization

Question 10

Effects of nicotine on CNS/PNS

Answer 10

• Beneficial: improved attention, memorization, decrease pain
• Both a stimulant and relaxant on skeletal muscle
• Activates the nucleus accumbens reward system of ventral striatum
• Can stimulate and subsequently desensitize receptors

Question 11

Nicotine concentrations in the blood vary depending on delivery method; cigarettes are most addictive, why?

Answer 11

cigs cause nicotine levels in blood to peak quickest and drops just as quick.

Question 12

2 types of receptors affected by nicotine:

Answer 12

Homomeric: alpha7; allow for influx of Ca2+
Heteromeric: alpha4/beta2; allow influx of Ca2+ and Na+
Both are activated by nicotine (nicotinic receptors), cause an increase in dopamine release.

Question 13

Nicotinic receptor desensitization (acute) by nicotine vs. cystine

Answer 13

• presence of nicotine causes a large inward current that quickly dissipates = desensitization of the receptor to nico
• Cysteine is an agonist of nicotinic receptor that causes a smaller inward current, but it lasts longer. So cysteine desensitization is slower. (thus, cystine is not addictive!)

Question 14

how does desensitization explain of receptors explain why nicotine is so addictive?

Answer 14

• nicotine activates nicotinic ACh receptors, causing dopamine release = reward pathway. - but current through the receptor dissipates quickly as receptors become desensitized (need more nico to activate these again–> addiction).