APP Module (GTown) - Addiction, Alcoholism, and Drugs of Abuse (Hrs 1 and 2)

Question 1

All drugs of abuse interfere in some way with what?

Answer 1

ventral striatum

Question 2

What is tolerance?

Answer 2

Decreased response to a repeated dose of substance over time; or the need to increase a dose to obtain a similar effect

Question 3

What are some withdrawal symptoms of alcohol?

Answer 3

• tremor
• seizure
• DTs

Question 4

What are the three factors which influence addiction?

Answer 4

• drug
• user (genetics)
• environment

Question 5

Per statistics, which substance seems to be the “most” addictive?

Answer 5

nicotine

Question 6

What is the typical human use pattern?

Answer 6

1) initial experimentation or use
2) repeated use
3) compulsive drug-seeking
4) abstinence

Question 7

What properties does alcohol have?

Answer 7

anxiolytic, hypnotic, and anesthetic properties

Question 8

How do you make beer?

Answer 8

1) Harvest some hops and barley.
2) Get some brewer’s yeast.
3) Get a container with some water and add the yeast with the barley and hops and then wait.

Question 9

What is the affinity of ethanol for interactions?

Answer 9

millimolar range

Question 10

What is the affinity of dopamine for its receptor?

Answer 10

nanomolar range

Question 11

What do the differing affinities of dopamine and ethanol mean?

Answer 11

Lower affinities mean you mean much less of the substance to produce a response

Question 12

What might be considered an intoxicating dose of ethanol?

Answer 12

Those above ~15mM (A moderately intoxicating blood alcohol level of 0.08% (80 mg/dl) is equivalent to an ethanol concentration of 17 mM.)

Question 13

What are some molecular characteristics of ethanol?

Answer 13

amphipathicity and ability to readily cross lipid membranes

Question 14

What are the main CNS effects of alcohol?

Answer 14

• inhibition of excitatory neurotransmission and enhancement of inhibitory neurotransmission
• DA release modulation
• disinhibition, ataxia, and sedation
• chronic use leads to tolerance, dependence, etc.

Question 15

How does alcohol mediate its effect on plasma membranes?

Answer 15

Alcohol intercalates itself between lipid molecules in the plasma bilayer and affects both the membrane fluidity as well as protein function

Question 16

What are the main brain regions affected by alcohol?

Answer 16

• mesolimbic DA system
• amygdala
• striatum
• hippocampus
• cortex/cerebellum

Question 17

What changes do you see in the brain of a chronic alcohol user?

Answer 17

↓ brain mass
↑ ventricle size
larger gaps between gyri and sulci

Question 18

What effect does alcohol have on the firing at a NMDA synapse?

Answer 18

Markedly attenuates the inward current usually seen with glutamate dosing

Question 19

What are the main channels which alcohol affects?

Answer 19

1) NMDA and kainate
2) GABA-A
3) nACh
4) 5-HT3

Question 20

What are the features of an NMDA receptor?

Answer 20

1) tetramer
2) binds glutamater and glycine as a co-agonist
3) voltage-dependent Mg2+ block
4) NR1 and NR2 subunits

Question 21

What type of receptors does alcohol seem to affect?

Answer 21

“cys-loop” family which includes nAChRs, 5-HT3, GABA-A

Question 22

How does alcohol affect GABA-A receptors?

Answer 22

potentiates flux of potassium ions

Question 23

Where are 5-HT3 receptors primarily expressed?

Answer 23

emetic centers of the brain

Question 24

What is Zofran?

Answer 24

Ondansetron is an anti-emetic which antagonizes 5-HT3 receptors

Question 25

Why is Zofran being used for alcohol abuse?

Answer 25

Seems to reduce cravings in early-onset alcoholics

Question 26

What are the six major receptor effects that alcohol has?

Answer 26

1) decrease in NMDAR activity 2) decrease in kainate receptor activity 3) decrease in voltage-sensitive calcium channels 4) increase in GABA-A activity 5) increase in 5-HT3 activity 6) increase in nAChR activity

Question 27

What do you see in fMRI images of intoxicated patients while performing a task?

Answer 27

Global depression of brain activity

Question 28

What are the four current pharmacological treatments for alcohol dependence?

Answer 28

1) disulfiram 2) naltrexone 3) acamprosate 4) long-acting naltrexone

Question 29

What is disulfiram and how does it work?

Answer 29

Disulfiram blocks the action of acetaldehyde dehydrogenase leading to an accumulation of acetaldehyde in the body which has a lot of unpleasant effects

Question 30

What is the treatment for acute methanol poisoning and how does it work?

Answer 30

Ethanol. Using ethanol actively competes for the alcohol dehydrogenase enzyme which in turn produces acetaldehyde instead of the far more toxic formaldehyde from methanol

Question 31

What is naltrexone and how does it work to treat alcohol abuse?

Answer 31

Naltrexone is an opioid receptor antagonist which decreases DA release associated with alcohol expectancy and consumption

Question 32

What is acamprosate and how does it work to treat alcohol abuse?

Answer 32

Acamprosate has complex effects on the glutamate-NMDA system and is also a GABA agonist. It seems to increase abstinence rates by working in opposition to the effects of alcohol

Question 33

What are some examples of Schedule I drugs?

Answer 33

- heroin - LSD - marijuana - MDMA - THG (an anabolic steroid)

Question 34

What are three requirements for a schedule I drug?

Answer 34

1) high potential for abuse 2) no currently accepted medical use 3) a lack of accepted safety for its use under medical supervision

Question 35

Can you prescribe Schedule I drugs as a physician?

Answer 35

Nope

Question 36

Who determines whether drugs are controlled and in which schedule they are put?

Answer 36

DEA, FDA, and congress

Question 37

What is the difference between desensitization and tolerance?

Answer 37

Sensitization is the increase in response to a repeated administration of drug. Tolerance is the decrease in a response to a repeated administration of a drug.

Question 38

What are some pharmacological effects of nicotine?

Answer 38

- facilitates memory - anxiolytic - anti-nociceptive properties - improves attention - both stimulant and relaxant

Question 39

What is the affinity of nicotine for the nicotinic receptor?

Answer 39

nanomolar range

Question 40

What are the two main subtypes of nicotinic receptor in the brain?

Answer 40

α7 homomeric receptor | α4β2 homomeric receptor

Question 41

What type of receptor is a nAChR?

Answer 41

pentameric ionotropic receptor

Question 42

What is the ion channel that the α4β2 receptor is associated with?

Answer 42

non-selective cation channel permeable to sodium and calcium

Question 43

Where are the nAChRs found in the brain?

Answer 43

dopaminergic neurons which reinforces the rewarding effect of nicotine

Question 44

What is activation of the nicotinic receptor characterized by in the presence of nicotine

Answer 44

rapid desensitization

Question 45

Why is cytisine not addictive like nicotine?

Answer 45

- no effect on increased receptor expression | - no desensitization at the receptor

Question 46

What is found regarding nicotinic receptors in post-mortem brain tissue

Answer 46

In chronic smokers, the nicotinic receptor has been upregulated

Question 47

What is special about the upregulation of receptors which nicotine causes?

Answer 47

It is not dependent on mRNA transcription which means nicotine is actively stabilizing and facilitating receptor expression directly

Question 48

What factors decrease nicotinic receptor expression in the brain?

Answer 48

- aging | - dementia and Alzheimer's

Question 49

How does varenicline work?

Answer 49

full agonist at the α7 receptor. partial agonist at the α4β2 receptor

Question 50

What are examples of some other pharmacological therapies for nicotine addiction?

Answer 50

- bupropion | - rimonabant (CB1R antagonist)

Question 51

How does the CB1R antagonist rimonabant exert its effect?

Answer 51

It's thought that chronic nicotine use leads to increased expression of CB1Rs in the mesolimbic system and antagonizing this lessens nicotine's rewarding effects

Question 52

What does alcohol do in conjunction with nicotine?

Answer 52

Alcohol potentiates the DA release of nicotine when used together

Question 53

How does cocaine work?

Answer 53

Inhibits DAT leading to increased concentrations of dopamine in the synapse for longer times

Question 54

What is a pharmacological effect seen with cocaine administration?

Answer 54

Sensitization. Increased response to repeated doses of cocaine and even generalization to associated and similar stimuli

Question 55

What effect does cocaine have on the neurons in the NAc?

Answer 55

Increased AMPA receptor expression. Change in shape and size of dendritic spines

Question 56

Who self-administers more cocaine on a daily basis if given the chance? Adolescents or adults

Answer 56

Adolescents!

Question 57

How does cocaine exert its local anesthetic effect?

Answer 57

inhibition of sodium channels

Question 58

What are the four receptor subtypes of opioid receptor?

Answer 58

mu, delta, kappa, and nociceptin

Question 59

What is the delta receptor in the brain involved with?

Answer 59

- pain relief - antidepressant effects - physical dependence

Question 60

What is the kappa receptor in the brain and spinal cord associated with?

Answer 60

- sedation - spinal analgesia - pupil constriction

Question 61

What is the mu receptor in the brain and spinal cord associated with?

Answer 61

- physical dependence - respiratory depression - euphoria - pupil constriction - supraspinal analgesia

Question 62

What is the nociceptin receptor in the brain and spinal cord associated with?

Answer 62

- appetite - depression and anxiety - development of tolerance to mu agonists

Question 63

What are some effects of the opiate system?

Answer 63

pain relief euphoria strong tolerance and withdrawal effects

Question 64

What is a mu agonist?

Answer 64

morphine

Question 65

What separates heroin from methadone?

Answer 65

Heroin has larger peaks and valleys during administration while methadone is longer-lasting leading to a more level concentration in the body

Question 66

What are some endogenous opiates?

Answer 66

- endorphins - dynorphin - enkephalins

Question 67

What types of molecules are the endogenous opiates?

Answer 67

neuropeptides

Question 68

How do the opioid receptors signal?

Answer 68

As GPCRs through the Gi signaling pathway

Question 69

What are the CNS endorphin pathways like?

Answer 69

similar to brain reward pathways

Question 70

What are some maintenance medications for opiate abuse?

Answer 70

- naltrexone | - methadone

Question 71

What is the active component of cannabis?

Answer 71

THC

Question 72

How many cannabinoid receptor types are there?

Answer 72

Two: CB1 and CB2

Question 73

What are some endogenous cannabinoids?

Answer 73

2-AG and anandamide

Question 74

Where is the CB1 receptor located?

Answer 74

Pretty much through the body and CNS/PNS

Question 75

Where is the CB2 receptor located?

Answer 75

immune system

Question 76

What type of receptors are the CB1 receptors?

Answer 76

GPCRs which signal through Gi and inactivate pre-synaptic calcium release

Question 77

What is the effect of CB1 receptor agonists?

Answer 77

Inhibition of motor performance

Question 78

Why do CB1R agonists affect motor movement?

Answer 78

Because they are highly expressed in the GP and striatum

Question 79

What is unique about the CB1 receptor?

Answer 79

It engages in retrograde signaling

Question 80

What is the effect of CB1 receptors in the hypothalamus linked to?

Answer 80

appetite regulation