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Neurobiology of Adult Brain Disorders > Addiction > Flashcards

Addiction Flashcards

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1
Q

Define addiction

A

a chronic and relapsing disorder that is characterized by a compulsive pursuit and consumption of a substance, an incapacity to control its intake, and a negative emotional state, disregarding any social, physical, or personal consequences

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2
Q

Dysfunction in circuits leads to characteristic __, __, and __ manifestations

A

biological, psychological, behavioral

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3
Q

There is a __ __ in rewarding stimuli, despite __ __

A

compulsive engagement
adverse consequence

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4
Q

What are the five characterizations of addiction

A

inability to consistently (A)bstain
impairment in (B)ehavioral control
(C)raving; or increased ‘hunger’ for drugs or rewarding experiences
(D)iminished recognition of significant problems with one’s behaviors and interpersonal relationships
Dysfunctional (E)motional response

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5
Q

What is the neurobiological definition of addiction?

A

a disorder that affects neurotransmission and interactions within reward structures of the brain

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6
Q

What areas of the brain are involved in addiction?

A

the nucleus accumbens (reward)
anterior cingulate cortex & PFC (judgement/ motivation)
basal forebrain (reward)
amygdala (emotions/ learning)

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7
Q

What are external cues for addiction?

A

trigger craving and drug use
increase the frequency of engagement in addictive behaviors

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8
Q

How does the hippocampus impact addiction?

A

brings back memory of previous euphoric or dysphoric experiences

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9
Q

How does the amygdala impact addiction?

A

triggers motivation of behaviors associated with past experiences

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10
Q

Define substance use disorder

A

a maladaptive patter of substance use leading to clinically significant impairment or distress

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11
Q

A substance use disorder is manifested by __ or more of the following, occuring in the same __ __ period; tolerance, withdrawal,, taken in larger amounts / over a longer period of time, persistent desire or unsuccessful efforts to stop, a great deal of time spent trying to obtain substance, changes in social, occupational, or recreational activities, or continued use despite knowledge of negative/ adverse side effect

A

three
12 month

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12
Q

What are the 7 possible manifestations of a substance use disorder?

A

tolerance
withdrawal
taken in larger amounts or over a longer period of time (reinforcement)
persistent desire or unsuccessful efforts to stop
a great deal of time spent in activities necessary to obtain the substance, use the substance, or recover from its effects
changes in social, occupational, or recreational activities
continued despite knowledge of negative/ adverse effects

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13
Q

Define the manifestations of tolerance

A

a. a need for markedly increased amounts to achieve intoxication or the desired effect
b. markedly diminished effect with continued use

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14
Q

Define the manifestations of withdrawal

A

a. the characteristic withdrawal syndrome
b. the same (or closely related) substance is taken

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15
Q

Define gambling addiction

A

persistent and recurrent problematic gambling behavior leading to clinically significant impairment or distress

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16
Q

In order to be diagnosed with a gambling addiction, an individual must exhibit __ of the following in a __ __ period

A

four; 12 month

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17
Q

What are the 8 possible manifestations of a gambling addiction?

A

gamble with increasing amounts of money
inability to cut down or stop gambling
preoccupied with gambling (thinking about it)
gambling when feeling distressed
returns another day to get even
denial and concealment
desperate financial situations
continued despite knowledge of negative/adverse effects

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18
Q

What are 5 psychological-behavioral-social components of addiction in adults?

A

alteration of the will
lack or poor awreness of disease
deficit of self-control
low tolerance to frustration
deficit to detect danger
decreased motivation
decreased self esteem
reduced social skills, anti-social behavior
emotional immaturity
irrational beliefs
violence
irrability
denial of personal essential needs (food, hygiene, physical apperance)

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19
Q

delta FosB is a __ __ factor, and a critical component and common factor in the development of virutally all forms of __ and __ addictions

A

gene transcription
behavioral; drug

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20
Q

What does FosB stand for?

A

FBJ murine osteosarcoma viral oncogene homolog B

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21
Q

Addiction arises, and the associated compulsive behavior intensifies or attenuates, along with…

A

the genetic overexpression of deltaFosB in the D1-type medium spiny neurons of the nucleus accumbens

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22
Q

What is used as an addiction biomarker?

A

DeltaFosB

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23
Q

What are examples of drug and behavioral addictions?

A

alcoholism
amphetamine
cocaine
nicotine
opiates
food
gambling
sex

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24
Q

Delta FosB expression in __ __ directly and positively regulates __ __ and __ __ through __ __ while decreasing sensitivity to __

A

D1 neurons
drug self-administration, reward sensitization
positive reinforcement
aversion

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25
Q

Describe the development of social use

A

social use —-(transient neuroplasticity)—> habitual use —(stable neuroplasticity)—> compulsive use

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26
Q

What are six side effects of withdrawal?

A

anxiety, insomnia, depression, nausea and vomiting, difficulty thinking, tachycardia, fatigue, agitation, sweating, nightmares, loss of appetite, hallucinations, headahces, seizures, tremors, and irritability

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27
Q

What are the two mechanisms of synaptic plasticity

A
  1. covalent modifications of existing synaptic proteins (protein phosphorylation)
  2. synaptic plasticity mediated by the activation of second messenger signals that regulate gene expression
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28
Q

What are the types of genes that are mediated by the activation of second messenger signals that regulate gene expression?

A

synaptic transmission
synthesis of cell process (neurites and dendrites)
cytoskeleton

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29
Q

Define alcoholism

A

pre-occupation or compulsion towards alcohol consumption associated with reduced capacity to recognize the negative effects of alcohol consumption

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30
Q

Describe the effects at 0.05 BAC

A

personality changes
relief from anxiety
social lubricant
disinhibition

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31
Q

Describe the effects at 0.08 BAC

A

significant disinhibition
impaired judgement, cognition
impaired motor coordination
sedation

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32
Q

Describe the effects at 0.15 BAC

A

incoherent speech
major motor impairment
reduced reaction time
black outs
hypnosis/ general anesthesia

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33
Q

Describe the effects at 0.30 BAC

A

increased sedation
approaching anesthesia
approaching coma

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34
Q

Describe the effects at 0.40 BAC

A

coma
lethal for 50% of people
death

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35
Q

What are the alcoholic limits for healthy men up to 65yo

A

no more than 4 drinks per day
no more than 14 drinks per week

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36
Q

What are the alcoholic limits for healthy women and men older than 65yo

A

no more than three drinks a day
no more than 7 drinks a week

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37
Q

What is the standard drink in the US?

A

any drink that contains about 0.6 fluid ounces or 14 grams of ‘pure’ alcohol

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38
Q

Describe the percent of ‘pure’ alcohol in standard drinks

A

12 fl oz beer = roughly 5% alcohol
8-9 fl oz of malt liquor = roughly 7%
5 fl oz of table wine = about 12% alcohol
1.5 fl oz of 80-proof spirits = about 40% alcohol

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39
Q

EtOH behavioral effects are similar to the effects of ?

A

GABA(A)-R agonists

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40
Q

Which subunit expressions are very sensitive to EtOH?

A

a1 and a4

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41
Q

Gabra4 and a4 proteins are __ by chronic EtOH in vivo and in vitro

A

up-regulated

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42
Q

EtOH induces the __ and __ __ of HSF1

A

nuclear translocation
activation

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43
Q

Transcription factor __ binds to the __ in Gabra

A

HSF1; ARE

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44
Q

__ is required for EtOH induction of Gabra4

A

HSF1

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45
Q

T/F: A constitutively transcriptionally active HSF1 construct, mimics EtOH effects

A

true

46
Q

Gabra4 minimal promotor is __, but not __ by __

A

functional
inducible, EtOH

47
Q

An extended construct containing __ and __ is necessary for EtOH sensitivity

A

E1 and 2

48
Q

What is an ARE?

A

alcohol responsive element
a novel consensus binding site for HSF1 present downstream the promotor of Gabra4

49
Q

EtOH induces the activation of __ in neurons

A

HSF1

50
Q

How does HSF1 induce gene expression?

A

by interacting with the alcohol responsive element (ARE)

51
Q

What are five proteins of calcium binding-calmodulin binding calcium dependent phospholipid binding?

A

synaptotagmin I, neurogranin, spectrin beta 2, transcript variant 1, cadherin 13

52
Q

What are three proteins of actin binding-cytoskeletal regulatory protein cytoskeleton organization?

A

microtubule-associated protein 1B, glycoprotein m6a, ELMO domain containing 1

53
Q

What is a protein of the secretory pathway, what is its function?

A

SEC23A (S. cerevisiae)
part of the COPII (coat protein II) secretory pathway

54
Q

What is a protein of cell growth regulation? What is its function?

A

glypican 5; cell surface heparan sulphate proteoglycan

55
Q

What is the function of synaptotagmin I?

A

synaptic vesicle-associated calcium binding protein

56
Q

What is the function of neurogranin?

A

neuronal-specific calcium sensitive calmodulin-binding protein

57
Q

What is the function of spectrin beta 2, transcription variant 1?

A

calcium sensor protein localized in axon terminals

58
Q

What is the function of cadherin 13?

A

mediates calcium dependent cell to cell adhesion

59
Q

What is the function of microtubule-associated protein 1B?

A

binds and stabilizes microtubules in neurons

60
Q

What is the function of glycoprotein m6a?

A

stress proteins involved in neurite/ filopodia outgrowth and synapse formation

61
Q

What is the function of ELMO domain containing 1?

A

cytoskeleton protein

62
Q

ARE is present in all of the following genes and is up-regulated by both __ and __

A

EtOH; HS
Gpm6a,
mtap1b,
nrgn,
Elmo1,
spnb2,
Gpc5,
Sec23a,
Syt1, and
Cdh13

63
Q

What mechanisms of neurobiological and functional adaptations that result in the state of alcohol dependence?

A

Acute EtOH activates the transcription of a set of genes containing a genetic element that makes them sensitive to the drug (ARE)

Alcohol regulates the expression of these genes by activating the Heat Shock Protein cascade and the transcription factor HSF1

The genes regulated by alcohol are involved in synaptic transmission and cytoskeleton organization (synaptogenesis) suggesting a new synaptogeneis

64
Q

Acute EtOH activates the __ of a set of genes containing a genetic element that makes them sensitive to the drug (__)

A

transcription; ARE

65
Q

Alcohol regulates the expression of these genes by activating the __ __ and the __ __

A

Heat shock protein cascade
transcription factor HSF1

66
Q

the genes regulated by alcohol are involved in __ __ and __ __ suggesting a new __

A

synaptic transmission, cytoskeleton organization, synaptogenesis

67
Q

Synaptotagmin 1(Syt1), a __ protein that binds __ to __

A

synaptic, calcium, directly trigger vesicle fusion

68
Q

EtOH activates the __ of key genes involved in __ __

A

expression; synaptic transmission

69
Q

These are __ __ genes that regulate the fusion of _- __ and hence the release of __

A

calcium sensitive; synaptic vesicles; neurotransmitters

70
Q

The regulation of these genes can explain the __ of certain brain circuits that will enforce the __ behavior

A

facilitation; addictive

71
Q

Taken together with the changes induced on genes related to cytoskeleton morphogenesis, we can assume that alcohol causes _- changes in the brain that result in __ consequences

A

anatomical; physiological

72
Q

What mechanisms of neurobiological and functional adaptations that result in the state of alcohol dependence?

A

EtOH activates the expression of key genes involved in the synaptic transmission

These are Ca sensitive genes that regulate the fusion of synaptic vesicles and hence the release of neurotransmitters

The regulation of these genes can explain the facilitation of certain brain circuits that will enforce the addictive behavior

Taken together with the changes induced on genes related to cytoskeleton morphogenesis, we can assume that alcohol causes anatomical changes in the brain that result in physiological consequences

73
Q

EtOH induces the __ of Hsp genes in __

A

transcription; astrocytes

74
Q

EtOH up-regulates __ protein expression in __

A

HSP; astrocytes

75
Q

EtOH induces HSF1 __ __ in __

A

nuclear translocation; astrocytes

76
Q

T/F: astrocytes are glial cells

A

true

77
Q

__ induces the expression of Hsp70 in astrocytes

A

KCl

78
Q

EtOH increases intracellular free __ in __

A

calcium, astrocytes

79
Q

What gene types are induced by EtOH and HS in astrocytes?

A

Acetyl-CoA and lipid metabolism
Oxido-reductase activity and generation of antioxidant enzymes
Genes involved in inflammation and immunity (cellular and humoral immune response)
Apoptosis
Calcium signaling
Regulation of transcription
Cell proliferation and regulation (insulin-like growth factor signaling)
Cytoskeleton
Glial cell-specific genes

80
Q

Since the CNS does not express __ __, ethanol is metabolized within __ by __ or __, a part of the microsomal ethanol oxidizing system, to generate __, __ and __

A

alcohol dehydrogenase
astrocytes
catalase, cytochome P450
NAP+, NADH, ROS

81
Q

In this metabolization process of alcohol, ethanol is initially metabolized to __ which is then converted to __ and __

A

acetaldehyde
acetate, acetyl-CoA

82
Q

EtOH __ the levels of Acetyl CoA in astrocytes

A

increases

83
Q

EtOH __ the levels of ROS in astrocytes

A

increases

84
Q

Describe the chemistry of marijuana

A

30 to 60 cannabinoids
D-9-tetrahydro-cannabionol, THC

85
Q

Describe the pharmacological effects of marijuana

A

partial agonist of the cannabinoid receptor CB1
CB2 receptor, mainly expressed in cells of immune response
the activation of CB G-protein coupled receptors results in a decrease in cAMP

86
Q

Where are CB-R receptors expressed?

A

cerebellum, hippocampus, cerebral cortex (especially cingulate, frontal, and parietal regions), nucleus accumbens, and basal ganglia

87
Q

What is the function associated with the cerebellum?

A

body movement coordination

88
Q

What is the function associated with the hippocampus?

A

learning and memory

89
Q

What is the function associated with the cerebral cortex?

A

higher cognitive functions

90
Q

What is the function associated with the nucleus accumbens?

A

reward

91
Q

What is the function associated with the basal ganglia?

A

movement control

92
Q

What are the physical short-term effects of marijuana?

A

relaxation to sedation
coughing/ lung irritation
some pain control
increase in appetite
loss in muscular coordination
decreased blood pressure
increased heart rate
decreased nausea

93
Q

What are some of the mental short-term effects of a mild to moderate dose of marijuana?

A

confusion
drowsiness
feelings of detachment and being aloof
difficulty in concentration
disrupts short term memory

94
Q

What are some of the mental short-term effects of a strong dose of marijuana?

A

stimulation
distortions of color/time/sound

95
Q

What are some of the mental short-term effects of a very strong dose of marijuana?

A

feelings of movement
visual hallucinations
hallucinations

96
Q

Describe cocaine

A

bitter, white, odorless crystalline powder
extracted and refined from the Coca plant
stimulant

97
Q

Describe the pharmacology of cocaine

A

blocking reuptake of catecholamines in the presynaptic neurons
increase in norepinephrine
increase in dopamine and serotonin
increase of cholinergic stimulation
blocking of sodium channels
local anesthetic

98
Q

List some of the physiological effects of cocaine

A

increased alertness
decreased fatigue
increased concentration
insomnia
increased irritability
increased psychosis
confused behavior
increased fear
extreme paranoia
severe anxiety attacks
hallucinations
aggressive behavior

99
Q

What are some of the physical effects of cocaine?

A

decreased appetite
increased body temperature
increased heart rate
dilated pupils
nausea/ vomiting
violent behavior
kidney failure
seizure and/or stroke
heart attack

100
Q

Morphine is a natural __ which makes __

A

alkaloid; heroin

101
Q

Codeine is a natural __ which can make __ or __

A

alkaloid; oxycodone, hydrocodone

102
Q

Thebaine is a natural __ which makes __

A

alkaloid
buprenorphine naloxone

103
Q

T/F: Semisynthetics make natural alkaloids

A

False, semisynthetics are DERIVED from natural alkaloids

104
Q

Morphine, codein, thebaine are all?

A

opoids

105
Q

Natural alkaloids make __ which bind to __ receptors to create __ -like symptoms

A

semisynthetics
opoid
morphine

106
Q

What brain areas are affected during opoid abuse?

A

nucleus accumbens, caudate nucleus, and thalamus

107
Q

What are the physiological effects of opioids?

A

drowsiness and lethargy
apathy
cognitive impairment
sense of tranquility

108
Q

Describe the depression of respiration effect of opioids

A

main cause of death from opioid overdose
alcohol potentiates its effect

109
Q

How do opioids work as a cough suppression?

A

opioids suppress the ‘cough center’ in the brain

110
Q

__ __ in the presence of analgesics is characteristic of opioid use

A

pupillary constriction

Neurobiology of Adult Brain Disorders (10 decks)

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