psychobiology of drug addiction Flashcards
1
Q
in 2021 how many drug related deaths were registered in England and Wales?
A
almost 5,000 deaths (according to office for national statistics)
2
Q
how is a drug addiction characterised?
A
- compulsion to seek out drug
- loss of control in limiting intake of drug
- negative emotions when access to drug is limited
3
Q
is addiction a chronically relapsing disorder?
A
yes, most people who suffer with addiction will relapse
4
Q
how does the DSM-V diagnose a substance use disorder?
A
- 11 criteria
- severity is determined based on the number of criteria the person meets
- mild = 2-3
- moderate = 4-5
- severe = >6
5
Q
when is someone most likely to get a diagnosis/ intervention?
A
when there starts to be impairment in day to day life
6
Q
how many people stay abstinent without treatment?
A
around 12%
7
Q
how many people stay abstinent with treatment?
A
around 30%
8
Q
what is the average relapse rate for substance abuse disorders?
A
40-60%
9
Q
do drugs impact neural circuits in the brain?
A
yes
10
Q
are certain drugs more addictive than others?
A
yes
11
Q
what is the learning process of addiction?
A
people become conditioned to a certain feeling and environment that is created from substance use (classical and operant conditioning)
12
Q
how is an impulse control disorder characterised?
A
- increased arousal before taking drug, regret after
- positive reinforcement
13
Q
how is a compulsive disorder characterised?
A
- relief from stress or anxiety due to compulsion
- negative reinforcement (negative feeling is take away from taking the drug)
14
Q
when might people with an addiction realise it has became a problem
A
when they no longer use the substance for pleasure but instead use it to feel like they can function normally again
15
Q
stages of addiction
A
- binge/ intoxication
- withdrawal/ negative affect
- preoccupation/ anticipation
16
Q
what is a possible explanation for why there is still such a high relapse rate with treatment?
A
treatments often do not target the mechanisms which lead to maladaptive behaviour
- usually try to modify behavioural symptoms when it may be the alterations in the brain that need treating
17
Q
do different drugs impact the brain differently?
A
yes, through different mechanisms
18
Q
what is the most common neurotransmitter that is influenced by drugs of abuse?
A
dopamine
19
Q
what is comorbidity?
A
when individuals meet criteria for 2 or more disorders
20
Q
what % of people receiving treatment for addiction also have another mental health disorder?
A
around 50-75%
21
Q
how many individuals with a mental health disorder currently has (or has previously had) a substance abuse disorder?
A
25-50%
22
Q
why can comorbidity be a problem?
A
it is difficult to determine which is causing the other, treatment should focus on the one that is causing the other
23
Q
what did Friedman et al, 2013 find?
A
that there is not a great level of agreement (kappa) between different clinicians when diagnosing a patient
24
Q
classical conditioning
A
associate an involuntary response with a stimulus
e.g. Pavlov’s dogs
25
operant conditioning
associate a voluntary behaviour with a consequence
e.g. Skinner box
26
positive reinforcement
behaviour followed by a reward
27
negative reinforcement
behaviour reinforced by taking away a negative stimulus as a result
28
positive reinforcement of drug use
the positive effects caused by the drug
29
negative reinforcement of drug use
more for addicted use - using the drug to take away the negative feelings of withdrawal
to take away a negative feeling
30
extinction in drug use
abstinence
31
definition of extinction in operant conditioning
disappearance of a conditioned response to a stimulus
32
meaning of spontaneous recovery in operant conditioning
the sudden reinstatement of a conditioned response to a stimulus
33
meaning of spontaneous recovery in relation to drug use
reinstatement of the conditioned response
relapse
34
spreading activation meaning in relation to drug use
associative process
may see a pub which may then remind the individual of drinking alcohol and the fun, reward, etc.
35
incentive salience
cognitive process that motivates an individual's behaviour to or away from a certain stimulus
36
high incentive salience
high incentive salience will elicit motivation to pursue that stimuli for the reward it provides
- drugs typically have higher incentive salience than other rewarding behaviours which motivates drug users to engage in drug seeking
37
incentive-sensitisation theory
theory that drug addiction is the amplification of psychological 'wanting' without necessarily increasing 'liking'
38
brain regions implicated in the incentive-sensitisation theory
neural changes after repeated drug use
- dopamine pathways in cortical regions linked to 'wanting'
- dopamine pathways in dorsal striatum/ midbrain linked to 'liking'
39
where is the ventral tegmental area (VTA) located?
midbrain
40
where is the nucleus accumbens (NAcc) located?
dorsal striatum
41
what neurotransmitter is released due to natural rewards?
dopamine
42
is cocaine a dopamine agonist?
yes
43
how does repeated drug use effect dopamine?
- decreases in dopamine release (may be less in the vesicles)
- decrease in DA2 receptors (downregulation)
- then become reliant on external sources (drugs) for enhanced DA release
44
what did Volkow et al. (2001) find when comparing PET scans of meth users and control participants?
- meth users had 24% less DA transporters in their striatum
- after 14 months abstinence, DA transporters increased back to normal levels
45
what is the striatum involved in?
decision making, habit formation and reward
46
how is allostasis related to drug addiction?
- previous reward point may have been changed by allostatic process
addicts may no longer gain satisfaction from natural rewards
47
what is allostasis?
allostasis is the maintenance if physiological state around a setpoint that has deviated from the body's normal setpoint
- process which changes the homeostatic setpoint
48
example of allostatic process in drug use
the dopamine level needed to feel reward may be raised in someone with an addiction
- repeated drug use does this
- eventually everyday things are no longer rewarding (anhedonia)
49
how do allostatic changes lead to craving and drug seeking behaviour?
- brain adapts to new dopamine levels due to repeated drug use
- when drugs are removed the reward circuits are 'underwhelmed'
- so this leads to negative reinforcement
- drugs to reduce unpleasant withdrawal symptoms
50
opponent-process theory of drug addiction (theoretical model)
- repeated drug use activates anti-reward processes
- A process = occurs first, fast acting effects of drug, euphoric effect
- B process = follows after, lasts longer, leads to withdrawal effects
- the countereffects by the body (B process) become stronger and quicker which leads to shorter/ weaker experience of the drug
51
what does the B process do in the opponent-process theory of drug addiction?
opposes the drugs immediate effects (A process)
52
what is the B process for alcohol?
glutamate
- excitatory neurotransmitter as alcohol is inhibitory
53
what is the B process for opioid?
glutamate/ substance P
54
what is the B process for cocaine?
GABA
- inhibitory neurotransmitter as cocaine is excitatory
55
what is glutamate?
the most abundant excitatory neurotransmitter
56
does context/ environment play a role in B process (opponent-process theory)?
yes, in a certain environment due to associative learning the body may start releasing enzymes/ start its countereffects before you even take the drug
- how often overdose occurs in unfamiliar environment
57
what enzyme is released to break down alcohol?
alcohol dehydrogenase
- this is a B process in the body for alcohol
58
how does context environment effect the impact of drugs?
- if you always consume drugs in a certain environment associative learning allows the body to start the B process before you even take the drug
- so you would have a stronger tolerance for the drug in that environment
-if you take the same amount of drug in an unfamiliar environment then it will have stronger effects
59
study on rats that shows how environment can impact B processes/ cause overdose?
- rats were injected with heroin in a certain cage
- build up a tolerance in this environment
- then the cages were swapped and the death rate of the rats doubled from 32.4% to 64.3%
(old study, 1982)
60
self-control model of addiction
behavioural control and inhibition is limited
- exerting control is an effort which causes fatigue and stress
- this then leads to stress-induced craving/ reinstatement
61
what did Ferrari et al. (2009) find?
higher trait self-control was a predictor of abstinence from alcohol abuse, greater impulse control
- showing self-control is important component to prevent relapse
62
areas of the brain involved in self-control
- orbitofrontal cortex (OFC)
- dorsolateral PFC (dlPFC)
- anterior cingulate cortec (ACC)
63
what was found by Wagner et al. (2013) in relation to self-control and the brain?
study looking at lack of self-control, used fMRI to look at a control vs. depleted group
- increased sensitivity to rewarding stimuli (OFC)
- decreased connectivity between OFC and dlPFC
- reduced inhibition
- poorer risk assessment and decision making
64
what did Inzlicht et al. (2007) find in relation to self-control and the brain?
- looked at control vs. depleted groups
- EEG
- diminished ACC activity (diminished impulse control)
- less likely to detect errors in their behaviour
65
where do most neurotransmitters start and project out from?
the midbrain
66
areas of the midbrain involved in addiction
- dorsal raphe nucleus (DRN)
- ventral tegmental area (VTA)
- substantia nigra (SN)
67
ventral tegmental area (VTA) in addiction
- 'origin' of reward pathways
- dopamine projections
68
substantia nigra (SN) in addiction
- reward seeking
- dopamine
69
areas of the forebrain involved in addiction (subcortical structures)
- thalamus
- hypothalamus
- hippocampus
- amygdala
- basal ganglia (several structures: NAcc particularly)
- anterior cingulate cortex
70
what is the role of the hypothalamus?
homeostasis
71
what is the role of the hippocampus?
memory
72
what is the role of the thalamus?
relay, signals go through the thalamus
73
what is the role of the amygdala?
consolidates emotional memories (rewarding behaviours)
74
what is the role of the nucleus accumbens (NAcc)?
- works to make sure we don't forget rewarding stimuli
- reinforcement
- stimulated by the VTA
- key role in addiction
75
what is the role of the anterior cingulate cortex?
- impulse control
- modulates emotional response
- reward anticipation
76
areas of the forebrain involved in addiction
- dorsolateral PFC (dlPFC)
- medial PFC (mPFC)
- ventrolateral PFC (vlPFC)
- obitofrontal cortex (OFC): ventromedial PFC
77
what is the role of the dorsolateral PFC in addiction?
- response selection
- decision making and planning
- risk assessment
78
what is the role of the medial PFC in addiction?
- retrieval of prior memories
- reinstatement of drug seeking behaviour
79
what is the role of the ventrolateral PFC in addiction?
inhibition
80
what is the role of the ventromedial PFC in addiction?
- assigns value to behaviour
- estimates risk/ benefit
- decision making
81
which brain areas are involved in the self-control network?
- dorsal anterior cingulate cortex (dACC) (conflict processing)
- mPFC (memory retrieval)
- rostral anterior cingulate cortex (rACC) (monitoring external cues)
- dlPFC (response selection)
82
which dopamine pathway is considered the start of addiction?
mesolimbic
83
which dopamine pathway is considered to lead to the pursuit of drugs?
mesocortical
84
mesolimbic dopamine pathway
- cell bodies in VTA, axons terminate in limbic system
- nucleus accumbens (NAcc), amygdala and hippocampus
85
mesocortical dopamine pathway
- cell bodies in VTA, axons terminate in PFC
- motivation, behaviour planning and emotion regulation
86
corticolimbic dopamine pathway
- connections between PFC and limbic system
- guides motivation and drug seeking
87
pharmacokinetics
refers to how drugs pass through the body
87
pharmacodynamics
refers to the physiological actions of drugs
88
agonist drug
mimics neurotransmitter (high affinity to receptor) or increases prevalence/ effectiveness of natural neurotransmitters
89
antagonist drug
blocks receptor to reduce effectiveness or decreases prevalence/ availability of natural neurotransmitter
90
upregulation of receptors
increased receptors in postsynaptic neuron
91
downregulation of receptors
decreased receptors in postsynaptic neuron
- chronic drug use can downregulate receptors = less sensitivity to the effects of NTs (tolerance)
92
which DA receptors are excitatory?
D1 and D5
93
which DA receptors are inhibitory?
D2, D3 and D4
94
meso =
midbrain
95
role of norepinephrine and epinephrine
promotes arousal and attention
96
role of serotonin (5HT)
regulates mood, reduces anxiety
97
role of acetylcholine (ACh)
- arousal and attention
- learning and memory
- receptors - nicotinic and muscarinic
98
endocannabinoids
- produced by the body
- involved in learning and memory
- regulation of emotions
99
processes involved in how drugs pass through the body (pharmacokinetics)
absorption
distribution
biotransformation
elimination
100
what is the fastest route of drug administration?
intravenous
straight into the bloodstream
101
bioavailability of drug
how much of the drug administered actually reaches its target (receptor)
102
non-competitive antagonist
drug that does not bind to the same site as a neurotransmitter, but does prevent the neurotransmitter from activating the receptor
103
competitive antagonist
drug that binds to the same site as a neurotransmitter, preventing a neurotransmitter from binding to the receptor
104
non-competitive allosteric antagonist
means the chemicals no longer fit the receptor
105
allosteric regulators
- substance that binds to site on receptor and causes changes
- non-competitive
- can be agonist or antagonist
106
positive allosteric modulator
substance that increases receptor affinity
107
negative allosteric modulator
substance that decreases receptor affinity
108
which receptors are common targets for positive or negative modulators?
GABA A receptors
- benzodiazepines enhance binding affinity for GABA, increasing the likelihood that NTs will bind (positive modulator)
- GABA is the primary inhibitory NT
109
sensitisation in chronic drug use
adaptation that increases a drugs effects
110
tolerance in chronic drug use
adaptation that reduces a drugs effects
- meaning higher doses are required to achieve desired effects
111
pharmacokinetic tolerance (drug dispositional tolerance)
- chronic use of a drug resulting in faster metabolism
- reductions in the amount of drug reaching its action site
- increased rate of drug to metabolites
112
pharmacodynamic tolerance
- reduced responsiveness at drug site of action
- occurs due to change in number of receptors available to bind
113
cross-tolerance
chronic use of one drug can result in tolerance of another drug with similar structure
- i.e. those addicted to heroin can tolerate a high dose of morphine
114
biotransformation
- what happens to a drug after they enter the bloodstream and before they leave the body
- lipid-soluble drugs must be transformed into metabolites
115
phase I biotransformation
- cytochrome P450 enzymes catalyse reactions to biotransform the drug and make it less active and more hydrophilic
- via oxidation, reduction or hydrolysis
116
phase II biotransformation
- conjunction
- combining the drug with another molecule
- often adding glucuronic acid
- aim is to make the drug hydrophilic enough to be excreted
117
where are the cytochrome P450 enzymes located?
in the hepatocytes in the liver and a few in the cells that line the GI tract
- these are the main system involved in drug metabolism
118
do more lipid-soluble drugs get absorbed quicker than less lipid-soluble drugs?
yes
119
half-life
time taken for the body to eliminate half the concentration of a drug
120
cannabinoids
substances that act on cannabinoid receptors
121
what is the psychoactive component in cannabis
THC
122
endocannabinoids
naturally occurring, similar to cannabinoids
123
what are endocannabinoids involved in?
learning, memory, emotional regulation and biological functioning
- which is why cannabinoids can effect these things
124
how to cannabinoids influence dopamine?
- activation of CB1 receptors in the brain and periphery leads to increased DA concentrations in the NAcc
- this is indirect effect as they inhibit GABA neurons which then increases the activity of DA neurons, meaning they release more DA
125
where does the reward during initial drug use come from?
comes from dopamine activity in the nucleus accumbens
- intense rewarding feeling so encoded as a strong memory
126
what are the two components of the NAcc?
shell (liking) and core (wanting)
127
what is the shell of the nucleus accumbens connected to?
VTA and hippocampus
- conditioning and learning
128
what is the core of the nucleus accumbens connected to?
with the anterior cingulate cortex (ACC) and OFC
- motivation and goal-oriented behaviour
129
direct dopamine agonists
- trigger dopamine release
- block dopamine reuptake
130
drugs that are direct dopamine agonists
amphetamines
cocaine
MDMA
131
indirect dopamine agonists
- leads to dopamine release by activating other NT receptors
132
examples of drugs that are indirect dopamine agonists
nicotine (acetylcholine)
alcohol (GABA)
THC (cannabinoid)
133
examples of drugs that impact serotonin
amphetamines
cocaine
LSD
134
examples of drugs that impact noradrenaline
amphetamines
cocaine
135
examples of drugs that impact acetylcholine
nicotine (direct)
caffeine (lesser effect, indirect)
136
pharmacokinetics
basic principles of drug absorption, distribution, metabolism, and excretion
137
