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Neurobiology of Adult Brain Disorders > Addiction > Flashcards

Addiction Flashcards

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
Describe the development of social use
social use ----(transient neuroplasticity)---> habitual use ---(stable neuroplasticity)---> compulsive use
26
What are six side effects of withdrawal?
anxiety, insomnia, depression, nausea and vomiting, difficulty thinking, tachycardia, fatigue, agitation, sweating, nightmares, loss of appetite, hallucinations, headahces, seizures, tremors, and irritability
27
What are the two mechanisms of synaptic plasticity
1. covalent modifications of existing synaptic proteins (protein phosphorylation) 2. synaptic plasticity mediated by the activation of second messenger signals that regulate gene expression
28
What are the types of genes that are mediated by the activation of second messenger signals that regulate gene expression?
synaptic transmission synthesis of cell process (neurites and dendrites) cytoskeleton
29
Define alcoholism
pre-occupation or compulsion towards alcohol consumption associated with reduced capacity to recognize the negative effects of alcohol consumption
30
Describe the effects at 0.05 BAC
personality changes relief from anxiety social lubricant disinhibition
31
Describe the effects at 0.08 BAC
significant disinhibition impaired judgement, cognition impaired motor coordination sedation
32
Describe the effects at 0.15 BAC
incoherent speech major motor impairment reduced reaction time black outs hypnosis/ general anesthesia
33
Describe the effects at 0.30 BAC
increased sedation approaching anesthesia approaching coma
34
Describe the effects at 0.40 BAC
coma lethal for 50% of people death
35
What are the alcoholic limits for healthy men up to 65yo
no more than 4 drinks per day no more than 14 drinks per week
36
What are the alcoholic limits for healthy women and men older than 65yo
no more than three drinks a day no more than 7 drinks a week
37
What is the standard drink in the US?
any drink that contains about 0.6 fluid ounces or 14 grams of 'pure' alcohol
38
Describe the percent of 'pure' alcohol in standard drinks
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
39
EtOH behavioral effects are similar to the effects of ?
GABA(A)-R agonists
40
Which subunit expressions are very sensitive to EtOH?
a1 and a4
41
Gabra4 and a4 proteins are __ by chronic EtOH in vivo and in vitro
up-regulated
42
EtOH induces the __ and __ __ of HSF1
nuclear translocation activation
43
Transcription factor __ binds to the __ in Gabra
HSF1; ARE
44
__ is required for EtOH induction of Gabra4
HSF1
45
T/F: A constitutively transcriptionally active HSF1 construct, mimics EtOH effects
true
46
Gabra4 minimal promotor is __, but not __ by __
functional inducible, EtOH
47
An extended construct containing __ and __ is necessary for EtOH sensitivity
E1 and 2
48
What is an ARE?
alcohol responsive element a novel consensus binding site for HSF1 present downstream the promotor of Gabra4
49
EtOH induces the activation of __ in neurons
HSF1
50
How does HSF1 induce gene expression?
by interacting with the alcohol responsive element (ARE)
51
What are five proteins of calcium binding-calmodulin binding calcium dependent phospholipid binding?
synaptotagmin I, neurogranin, spectrin beta 2, transcript variant 1, cadherin 13
52
What are three proteins of actin binding-cytoskeletal regulatory protein cytoskeleton organization?
microtubule-associated protein 1B, glycoprotein m6a, ELMO domain containing 1
53
What is a protein of the secretory pathway, what is its function?
SEC23A (S. cerevisiae) part of the COPII (coat protein II) secretory pathway
54
What is a protein of cell growth regulation? What is its function?
glypican 5; cell surface heparan sulphate proteoglycan
55
What is the function of synaptotagmin I?
synaptic vesicle-associated calcium binding protein
56
What is the function of neurogranin?
neuronal-specific calcium sensitive calmodulin-binding protein
57
What is the function of spectrin beta 2, transcription variant 1?
calcium sensor protein localized in axon terminals
58
What is the function of cadherin 13?
mediates calcium dependent cell to cell adhesion
59
What is the function of microtubule-associated protein 1B?
binds and stabilizes microtubules in neurons
60
What is the function of glycoprotein m6a?
stress proteins involved in neurite/ filopodia outgrowth and synapse formation
61
What is the function of ELMO domain containing 1?
cytoskeleton protein
62
ARE is present in all of the following genes and is up-regulated by both __ and __
EtOH; HS Gpm6a, mtap1b, nrgn, Elmo1, spnb2, Gpc5, Sec23a, Syt1, and Cdh13
63
What mechanisms of neurobiological and functional adaptations that result in the state of alcohol dependence?
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
Acute EtOH activates the __ of a set of genes containing a genetic element that makes them sensitive to the drug (__)
transcription; ARE
65
Alcohol regulates the expression of these genes by activating the __ __ and the __ __
Heat shock protein cascade transcription factor HSF1
66
the genes regulated by alcohol are involved in __ __ and __ __ suggesting a new __
synaptic transmission, cytoskeleton organization, synaptogenesis
67
Synaptotagmin 1(Syt1), a __ protein that binds __ to __
synaptic, calcium, directly trigger vesicle fusion
68
EtOH activates the __ of key genes involved in __ __
expression; synaptic transmission
69
These are __ __ genes that regulate the fusion of _- __ and hence the release of __
calcium sensitive; synaptic vesicles; neurotransmitters
70
The regulation of these genes can explain the __ of certain brain circuits that will enforce the __ behavior
facilitation; addictive
71
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
anatomical; physiological
72
What mechanisms of neurobiological and functional adaptations that result in the state of alcohol dependence?
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
EtOH induces the __ of Hsp genes in __
transcription; astrocytes
74
EtOH up-regulates __ protein expression in __
HSP; astrocytes
75
EtOH induces HSF1 __ __ in __
nuclear translocation; astrocytes
76
T/F: astrocytes are glial cells
true
77
__ induces the expression of Hsp70 in astrocytes
KCl
78
EtOH increases intracellular free __ in __
calcium, astrocytes
79
What gene types are induced by EtOH and HS in astrocytes?
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
Since the CNS does not express __ __, ethanol is metabolized within __ by __ or __, a part of the microsomal ethanol oxidizing system, to generate __, __ and __
alcohol dehydrogenase astrocytes catalase, cytochome P450 NAP+, NADH, ROS
81
In this metabolization process of alcohol, ethanol is initially metabolized to __ which is then converted to __ and __
acetaldehyde acetate, acetyl-CoA
82
EtOH __ the levels of Acetyl CoA in astrocytes
increases
83
EtOH __ the levels of ROS in astrocytes
increases
84
Describe the chemistry of marijuana
30 to 60 cannabinoids D-9-tetrahydro-cannabionol, THC
85
Describe the pharmacological effects of marijuana
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
Where are CB-R receptors expressed?
cerebellum, hippocampus, cerebral cortex (especially cingulate, frontal, and parietal regions), nucleus accumbens, and basal ganglia
87
What is the function associated with the cerebellum?
body movement coordination
88
What is the function associated with the hippocampus?
learning and memory
89
What is the function associated with the cerebral cortex?
higher cognitive functions
90
What is the function associated with the nucleus accumbens?
reward
91
What is the function associated with the basal ganglia?
movement control
92
What are the physical short-term effects of marijuana?
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
What are some of the mental short-term effects of a mild to moderate dose of marijuana?
confusion drowsiness feelings of detachment and being aloof difficulty in concentration disrupts short term memory
94
What are some of the mental short-term effects of a strong dose of marijuana?
stimulation distortions of color/time/sound
95
What are some of the mental short-term effects of a very strong dose of marijuana?
feelings of movement visual hallucinations hallucinations
96
Describe cocaine
bitter, white, odorless crystalline powder extracted and refined from the Coca plant stimulant
97
Describe the pharmacology of cocaine
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
List some of the physiological effects of cocaine
increased alertness decreased fatigue increased concentration insomnia increased irritability increased psychosis confused behavior increased fear extreme paranoia severe anxiety attacks hallucinations aggressive behavior
99
What are some of the physical effects of cocaine?
decreased appetite increased body temperature increased heart rate dilated pupils nausea/ vomiting violent behavior kidney failure seizure and/or stroke heart attack
100
Morphine is a natural __ which makes __
alkaloid; heroin
101
Codeine is a natural __ which can make __ or __
alkaloid; oxycodone, hydrocodone
102
Thebaine is a natural __ which makes __
alkaloid buprenorphine naloxone
103
T/F: Semisynthetics make natural alkaloids
False, semisynthetics are DERIVED from natural alkaloids
104
Morphine, codein, thebaine are all?
opoids
105
Natural alkaloids make __ which bind to __ receptors to create __ -like symptoms
semisynthetics opoid morphine
106
What brain areas are affected during opoid abuse?
nucleus accumbens, caudate nucleus, and thalamus
107
What are the physiological effects of opioids?
drowsiness and lethargy apathy cognitive impairment sense of tranquility
108
Describe the depression of respiration effect of opioids
main cause of death from opioid overdose alcohol potentiates its effect
109
How do opioids work as a cough suppression?
opioids suppress the 'cough center' in the brain
110
__ __ in the presence of analgesics is characteristic of opioid use
pupillary constriction

Neurobiology of Adult Brain Disorders (10 decks)

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