L7 - ALCOHOL

Question 1

What is wrong with “alcoholism”?

Answer 1

Term used to describe AUD, a medical disorder with a recognized diagnosis.

Question 2

What does AUDIT stand for?

Answer 2

Alcohol Use Disorder Identification Test

Question 3

Describe the trajectory of alcohol effects in terms of sedation and stimulation according to dosage.

Answer 3

At low dose:
1. Relaxation
2. Disinhibition

At moderate dose:
Loosing the stimulant properties.

At high dose:
1. Impaired motor function
2. Stupor (“pass out”)
3. Coma
4. Death

Question 4

What is the reward phase of alcohol consumption neurobiologically characterized by?

Answer 4

DA, 5-HT and NE release

Question 5

How does alcohol modulate the release of DA?

Answer 5

Likely via an opioid peptide, alcohol disinhibits GABA control over VTA DAergic neurons.

Question 6

Neurobiologically, what is alcohol tolerance likely to signify for the mesolimbic pathway?

Answer 6

Regulation of GABA receptors is significant in the acquiring of tolerance.

Question 7

What are collateral neurobiological implications of binge-drinking apart from GABAr regulation?

Answer 7

Also adaptations in DA + glutamate neurons + endocannabinoid systems.

Question 8

How does alcohol tolerance put the health at risk?

Answer 8

Increased drug intake is necessary to produce reward, adverse health effects are coincidentally more likely.

Question 9

On which subregions of the extended amygdala is ethanol acting on?

Answer 9

-NAcc
-Bed Nucleus of the Stria Terminalis (BNST)
-Central nucleus of Amygdala

Question 10

List three neurobiological consequences of being in a withdrawal phase from alcohol.

Answer 10

-Activation of central amygdala stress circuit
-Decreased levels of DA, 5HT, enkephalin (opioid peptide involved in stress response) an endocannabinoids
-Increased levels of CRF (involved in stress response), dynorphin (opioid peptide), orexin (arousal), substance P (stress response)

Question 11

True or false: VTA GABA neurons are significant in the withdrawal phase of AUD.

Answer 11

True.

Question 12

Name 2 major psychological consequences of being in a withdrawal phase from alcohol.

Answer 12

-Negative affect (anxiety, depression and anhedonia)
-Increased salience for drug and decreased sensitivity to natural reinforcers

Question 13

What are the two metabolizers charged of degrading ethanol under normal conditions?

Answer 13

ADH (alcohol dehydrogenase)
ALDH (acetaldehyde dehydrogenase)

Question 14

In how many steps is ethanol metabolized?

Answer 14

2

Question 15

On what molecular structures is the metabolizing of ethanol dependent under normal circumstances?

Answer 15

NAD and mitochondrial electron transport chain

Question 16

When metabolizing reactions depending on NAD and the mitochondrial electron transport chain fail under excessive demand, what is metabolizing ethanol? What is the consequence?

Answer 16

Peroxisomes. Toxic oxygen radicals are produced and there is an accumulation of aldehyde = “hang over” state.

Question 17

Where are ADH and ALDH mostly expressed?

Answer 17

Liver, digestive tract.

Question 18

Why can it be counter-intuitive to characterize ethanol as a sedative?

Answer 18

Stimulatory effects at low dose.

Question 19

In the alcohol addiction phase of regulated relapse, what neurobiological component is driving excessive drug taking?

Answer 19

Significant changes in NMDA and AMPA receptors.

Question 20

True or false: during the regulated relapse phase of alcohol addiction, the midbrain stress system is becoming increasingly active.

Answer 20

True.

Question 21

What are the CRF and NPY systems standing for? How are they respectively regulating stress-induced relapse? During the withdrawal phase, how are the two systems comparing in terms of activity?

Answer 21

The corticotropin-releasing factor system is promoting the stress-induced relapse and the neuropeptide Y system is blocking the stress-induced relapse. During the withdrawal phase of AUD, the CRF system overweights the NPY system.

Question 22

Neurobiological structures from which brain area are particularly involved in compulsive drug seeking?

Answer 22

PFC

Question 23

What neurobiological structure is underlying PFC control over DA release in the NAcc?

Answer 23

GLUergic neurons

Question 24

What system is hypersensitive during withdrawal periods of AUD, GABAergic or GLUergic?

Answer 24

GLU system is hypersensitive and that has repercussions on GABA levels.

Question 25

True or false: CB1 is a molecular target of ethanol.

Answer 25

True.

Question 26

List the 6 neuronal types that are characterized as molecular targets of ethanol.

Answer 26

-GABAergic -GLUergic -DAergic -CRF neuron -Opioid neuron -Cholinergic neuron

Question 27

True or false: D1 but not D2 is a molecular target of ethanol.

Answer 27

False: D2 as well.

Question 28

Provide one clinical issue concerning the diagnosis of AUD.

Answer 28

Two recognized classifications of AUD: -ICD-10 (WHO): recognizing harmful use of alcohol + hazardous use of alcohol -DSM V (APA): integrates all cases under the spectrum of "AUD" (mild, moderate, severe)

Question 29

What are the cardinal features of AUD found in the DSM V and ICD-10 diagnoses of AUD.

Answer 29

-Pathological use of alcohol (behavioural criteria) -Preoccupying social or legal consequences -Tolerance and withdrawal

Question 30

List 5 medical complications objectively recognized to be associated with AUD.

Answer 30

-Cirrhosis (liver disease) -Cardiomyopathy (heart struggling to pump blood to the rest of the body) -Peripheral neuropathy (damage to PNS nerves) -Cerebellar degeneration -Dementia

Question 31

List 6 behavioural criteria for AUD.

Answer 31

-Daytime and morning intoxication -Unsuccessful efforts to reduce SU -Increased salience for drug -Beneficial activities abandoned to SU -Increased use despite physical impairments -Complication of intoxication

Question 32

True or false: fetal alcohol spectrum disorders are usually only discovered at puberty.

Answer 32

True (expect for FASD cases with malformations).

Question 33

Name two behavioural or psychological impairments resulting from fetal alcohol spectrum disorders.

Answer 33

Learning impairment (cognitive) and impulsivity, depression (affective disturbances).

Question 34

What is the most common comorbid psychiatric condition to AUD?

Answer 34

Nicotine addiction.

Question 35

List 2 psychiatric conditions that are susceptible to be secondary outcomes to AUD.

Answer 35

-Anxiety -Depression

Question 36

List 3 behavioural treatments for AUD.

Answer 36

-CBT (only woks if you WANT to stop drinking) - AA (12-step) -Motivational interviewing

Question 37

List 3 approved pharmacological interventions for AUD.

Answer 37

-Disulfuram: blocks ALDH (aversive) -Naltrexone: prevents GABA disinhibition on NAcc DA (mu-receptor antagonist) release by blocking opioid release = decrease DA release -Acamprosate (not always reliable): GABA-A receptor antagonist

Question 38

What is the single most determinant predictor of developing AUD?

Answer 38

Having a first-degree alcoholic relative.

Question 39

Is AUD a complex or simple Mendelian trait?

Answer 39

Complex, of course!

Question 40

What makes us think that there is genetic predisposition to AUD?

Answer 40

MZ twins tend to be more concordant that DZ. And 1° relatives tend be more concordant than 2° relative as well.

Question 41

Is AUD all about genetics?

Answer 41

No, environmental and personality components too.

Question 42

What are the two most known families of aldehyde hydrogenase (ALDH) genes?

Answer 42

AlDH-1 (cytoplasmic) AlDH-2 (mitochondrial)

Question 43

Polymorphic variation in which gene of aldehyde hydrogenase is associated with low alcohol consumption and a substantially reduced risk of alcoholism?

Answer 43

ALDH-2

Question 44

How are Caucasians and East Asians differentiating in terms of ALDH cytosolic isozyme (-1) and mitochondrial isozyme (-2) expression?

Answer 44

Most Caucasians have two major isozymes, while approximately 50% of East Asians have the cytosolic isozyme but not the mitochondrial isozyme (polymorphic variation at ALDH-2).

Question 45

Linkage studies of familial alcoholism implicate the ADH region of which chromosome?

Answer 45

Chromosome 4

Question 46

What are the three main structures of the midbrain stress system that are activated by ethanol?

Answer 46

-Central Nucleus of the Amygdala (CeAmyg) -Bed Nucleus of the Stria Terminalis (BNST) -Nucleus Accumbens Shell (NaccS)

Question 47

Provide a function to the following peptides: -Enkephalin -CRF -Dynorphin -Orexin -Substances P

Answer 47

-Enkephalin: mediating nociception by binding to opioid receptors -CRF (corticotropin-releasing factor): neuropeptides activating the HPA axis -Dynorphin: opioid peptide -Orexin: arousal, wakefulness -Substances P: involved in stress response

Question 48

What are the neuropeptides involved in the central amygdala microcircuitry?

Answer 48

GABA CRF NPY

Question 49

What are the effects of CRF and NPY systems on GABA levels in the microcircuitry of the central amygdala? What are the resulting effects on stress and anxiety?

Answer 49

CRF system increases intra-CeA GABA = pro-stress and anxiogenic NPY system decreases intra-CeA GABA = anti-stress and anxiolytic

Question 50

What are the two systems hypersensitive in withdrawn individuals?

Answer 50

CRF and Glut.

Question 51

Signal from which neurotransmitter is mediating cravings?

Answer 51

Glutamate