lecture 30: behavioural and developmental aspects of drug dependence Flashcards
1
Q
What was an old drug campaign?
A
- was warning people about the harms of a new drug that was hitting the streets depraved
- mother so intoxicated can’t look after baby
- no one working
- someone died
- people selling stuff to buy drugs
- 1750s
- ad for gin
- gin lane vs beer street
- beer people are quite respectable
- people concerned about concentrated alcohol
- encapsulates discussion we continue to have around drugs in the public space
- fear campaign
- people often think of drugs as a moral issue
- weakness, choice etc
2
Q
What did people show with animals?
A
- if you gave animals the same drugs that people use you could actually get animals to work hard to get drugs
- early part of last century
- mills and olner in 1960s showed there was a discreet part of the brain that underpinned the reward part of this process
- will work so hard that they will not eat or drink
3
Q
What is the system?
A
- unpacked over the next 20-30 years
- dopaminergic system
- starts in VTA → nucleus accumbens → prefrontal cortex
- system is about reinforcement and learning
- what is important in terms of survival
- sleeping, drinking, sexual behaviour, nurturing young
- evolved to ensure survival species
- drugs are reinforcing because they have ability to hijack this system
- tricks brain into thinking this is an important behaviour that is essential to survival
4
Q
What is seen in the neurons that projection onto nucleus accumbens?
A
- vesicles full of dopamine
- post-synaptic membrane
5
Q
How do drugs like cocaine affect this process?
A
- increase levels of dopamine in the synaptic cleft
- do that by blocking reuptake sites
- more post-synaptic activation
6
Q
What is activation of the reward pathway by addictive drugs?
A
- all drugs of abuse work by increasing dopamine in the system
- but they don’t all do it in the same way
- either directly or indirectly cause dopamine increase
- cocaine blocks reuptake
- heroin works on VTA (normally switched off, herion binds opiate receptors, disinibition)
- cannabis binds CB1 receptors in VTA
- drugs that we like to use are reinforcing bc of dopamine
7
Q
Why do people normally take drugs?
A
- to feel good in a social scenario
- does that because it releases chemicals in our pleasure centre
- doesn’t explain why people continue to take drugs when they no longer have the same effect
- and when they start to have negative consequences/adverse outcomes
- dopamine story is critical for explaining first use but not addiction
8
Q
What have drug users said about their experience with drugs?
A
- william burroughs
- junk is not, like alcohol or weed, a means to increased enjoyment of life. junk is not a kick. it is a way of life
- charlie parker
- they can get it out of your blood, but they can’t get it out of your mind
- idea that essentially something happens within you that changes the way you think about drugs regardless of any detoxification
9
Q
What is substance dependence (DSM IV)?
A
- maladaptive pattern of use → clinically sig. impairment or distress, manifested by more than 3 of the following in 12 mth period:
- tolerance (physical/physiological dependence)
- withdrawal (physical/physiological dependence)
- expect to experience opposite effects of drug
- substance often taken in larger amounts/longer period than intended
- persistent desire/unsuccessful efforts to decrease/control substance use
- considerable time spent in activities necessary to obtain/use drug, or recover from drug effects
- important social/occupational/recreational activities given up because of substance use
- continued use despite knowledge of having persistent/recurrent physical/psychological problem caused/exacerbated by drug
10
Q
What are heroin relapse rates?
A
- relapse rates substantial, even after successful detoxification
- 42% use within days of leaving detox
- 66% re-addicted 6 months later
- 48% still using after 7 years, 12% dead, 5% in prison
11
Q
What does a model of addiction need to explain?
A
- intense cravings
- loss of control over use
- compulsive pattern of behaviour
- high rates of relapse
12
Q
What is patient report by obrien 1976?
A
- the patient was a 28 year old man with a 10 year history of opiate addiction
- he was married and the father of two children
- he reported that, while addicted, he was arrested and incarcerated for 6 months
- he reported experiencing severe withdrawal during the first 4 or 5 days in custody, but later, he began to feel well
- he gained weight, felt like a new man, and decided that he was finished with drugs
- he thought about his children and looked forward to returning to his former job
- on the way home after release from prison, he began thinking of drugs and feeling nauseated
- as the subway approached his stop, he began sweating, tearing from his eyes and gagging
- this was an area where he had frequently experienced opiate withdrawal symptoms while trying to acquire drugs
- as he got off the subway, he vomited onto the tracks
- he soon bought drugs, and was relieved
- the following day he again experienced craving and withdrawal symptoms in his neighbourhood and he again relieved them by injecting heroin
- the cycle repeated itself over the next few days and soon he became re-addicted
this process is linking environment/situation to feeling
conditioning
13
Q
What is conditioning in animals?
A
- get them to work for a drug
- introduce stimuli e.g. red light or sound
- pair drug reward with light
- secondary reinforcer
- shut off access to drug and will continue to press for red light (will lessen over time)
- cue will predict relapse too
14
Q
What is incentive sensitisation?
A
- idea that this system become sensitised to the effects of drugs or stimuli that predict drug reward
- so when you show certain situations, places, environments
- so when exposed to that stimulus even in the absence of drug dopamine is released
15
Q
What is hedonic allostasis?
A
- idea that the reward system resets
- after a great night out we feel a bit flat the next day because used all the dopamine the night before
- so what happens when you have a great night continually
- reward set points change
- gets harder and harder to get your systems to release dopamine and to get the same buzz
- things we naturally enjoy also affected
- the only thing that makes them feel normal is drug use
16
Q
What is seen in brain imaging studies looking at dopamine systems between drug abusers and control subjects
A
- drug abusers systems very diminished
17
Q
What is responsiveness to drug reinforcers vs natural reinforcers?
A
- comprehensive multi-method Ax:
- experiential (self-report)
- expressive (facial EMG)
- reflex modulation (PA reflex)
- cortical/attentional (startle-elicited ERP)
- looking at pictures
- heroin users cf normal were overresponsive to opiate related pictures and underresponsive to natural related pictures
- predicted later drug use
- not enjoying every day things
- hard to just ‘go and do something else’
18
Q
What regions light up when showing drug imagery?
A
- part of the mesocortical dopamine system
- orbital frontal cortex → critical role in terms of making choices about how you live your life, finneas gage, critical for weighing up short term vs long term consequences
- anterior cingulate cortex → part of the brain that keeps you on track with your goals
19
Q
What was seen in studies looking at the prefrontal orbital cortex?
A
- executive tasks (wisconsin card holding) → no difference
- gambling task → huge discrepancy, 4 decks of cards (2 decks are win small lose small but overall win, or 2 are win big lose big but overall lose), need to pick from the advantageous decks, learn over time, drug abusers over sample from the disadvantageous decks
- tell you they know they should pick from the other but they can’t help themselves
- cognitive awareness that they are making the wrong decision
20
Q
What was seen in studies looking at the anterior cingulate cortex?
A
- multisource interference task
- robust predictor of AC function
- pick the number that is wrong
- find that both control and heroin users activate AC
- to perform the same level of task as controls, opiate uses have to activate much more of the control network
- i.e. using more brain power to achieve the same outcomes
- what happens when additional stresses are added → how can one be expected to control behaviour when system is overloaded?
- number of errors and and activity of AC
- doesn’t matter how many mistakes it makes, in heroin users AC will not amp up, unlike in controls
21
Q
What are newer models of addiction?
A
- trying to differentiate between physical dependence and psychological dependence
- physical dependence is in areas of the brain stem, subserve withdrawal and tolerance process
- addiction is the mesocortical/mesolimbic symstem
- discrete areas of the brain
22
Q
Is it that drug use causes these problems or is that people vulnerable to addiction already have these problems?
A
- chicken and the egg
- this is the big question
23
Q
What was seen in brain imaging of adolescents with strong family history of alcoholism?
A
- alcoholism is one of the most inherited psychiatric conditions
- never used
- paired with aged-matched controls
- adolescents who’ve never had a drink but have a strong fam history are already doing poorer on some of these tasks
- orbitofrontal volumes in early adolescence predict initiation of cannabis use: a 4 year longitudinal and prospective study (smaller OC at age 12 predictive of cannabis use at 16)
- perhaps some of these deficits that we see are actually premorbid
24
Q
What is adolescent anhedonia?
A
- increase in negative affect in adolescents cf younger or older individuals (Larson and Asmussen, 1991)
- reports of feeling happy decrease by 50%
- increase in levels of self-reported ‘boredom’
- experience and expect to experience positive situations as less pleasurable
- of evolutionary importance?
- predisposed to pursue new appetitive reinforcers through increase in risk-taking and novelty-seeking (Spear, 2002)
- need to learn the tasks necessary for independent living
- are some kids more vulnerable to addiction because this system makes them more anhedonic
25
Q
What is seen in number of neurons at different ages?
A
- at birth: several neurons
- 6: first few years of life we are learning lots so brain grows enourmously, at age 6 about same size as an adult
- 14: developmental task is pruning away excessive connections in the brain, becomes more optimal and effecient
26
Q
Does this pruning happen in a uniform way?
A
- no
- starts at the back and comes forward
- limbic and emotions mature first
- but the part of the brain that controls behaviour etc/stop part - develops much much later
27
Q
Is the experience of drugs the same in adolescence and adulthood?
A
- no extremely different
- rat bar
- adolescents and adults drink in different ways
- if adults are allowed to drink daily they will only drink as much as if they could go only two or three days a week
- adolescents drink more than adults
- also drink more when they can only drink intermittently → more likely to binge
28
Q
What is seen on a tilt table?
A
- looks at issues of coordination
- know if we drink too much we have motor incoordination
- compared to adults, adolescent animals can drink a lot more before having the same adverse effects
- i.e. adolescents can party much harder than adults because they don’t have the same adverse effects → in terms of those that limit how much you use
29
Q
What is the problem with this?
A
- wiring is more vulnerable to effects of drugs
- hypothalamus → for the same amount of drug or alcohol, adolescents are much more impacted in terms of memory and learning function
- young people more vulnerable to alcohol-induced memory impairments
- blackouts common in young drinkers
- 772 college students (18-22 years)
- 51% reported blackouts
- associated with risky behaviours
- BAC 0.30%
30
Q
How does this impact the brain?
A
- not many studies
- adolescent-onset alcohol use disorder
- smaller hippocampus than healthy controls and it correlated with how much they were drinking
- all of these studies are cross sectional so difficult to know cause and effect
31
Q
What is interesting about tobacco?
A
- if you try and get an animal to take some nictone they won’t because they find it aversive
- the only way you can do it is if you make them nicotine dependent first by injecting them
- in contrast adolescents love nicotine → will keep pressing the lever for it
- if you don’t pick up smoking by your early 20s you are not likely to pick it up as an adult
- at no dose is nicotine neurotoxic to the brain
- adolescents, particularly females, are much more sensitive to the effects of nicotine on the brain
- much more likely to create syndromes of depression in animal models
- early onset smoking is associated with a whole range of poor depressive outcomes
32
Q
What are the key questions?
A
- what are the specific (and non-specific) effects of alcohol and other drugs on neurodevelopmental processes)
- are they similar or distinct for different classes of drugs?
- if there are neurobiological sequelae, do these reflect the cumulative effects of longer exposure, or is early adolescence a particularly sensitive period of development in which drug exposure has more pronounced effects on maturing neurobiological systems?
- is there consistent evidence for premorbid neurobiological vulnerabilities amongst early onset users, and if so, does substance use have a more severe impact on neuromaturational processes in this high-risk group?
33
Q
summary
A
- drugs of abuse are reinforcing because of their ability to activate the brain’s reward system
- chronic drug use leads to neuroadaptations associated with both physiological and psychological dependence
- neuroadaptations associated with addiction are particularly evident within the reward system and frontal regions, and may not fully recover with abstinence
- there is evidence of premorbid and neurobiological vulnerabilities in at-risk populations
- the adolescent brain may be more vulnerable to the neurotoxic effects of drugs during adolescence
