9 Neurobiology of addiction and treatments Flashcards Preview

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Flashcards in 9 Neurobiology of addiction and treatments Deck (38)

What three criteria used to distinguish addiction from normal use?

1. Craving or compulsion
2. Loss of control
3. Little concern for consequences


What recreational drugs are used most often in Australia?

85% used alcohol recently

9% are daily drinkers

20% smoked recently


What drug is responsible for most deaths per year in Australia?

Tobacco (15,050);
Alcohol (3,494);
Opiates (221);
Stimulants (17);
Cannabis (1)


Can a substance disorder exist without evidence of physiological dependence?

Yes, tolerance and withdrawal are only two of the seven criteria for substance disorder


What are the DSM criteria for substance abuse disorder?

A maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by three of the following, occurring at any time in the same 12-month period:
1. Tolerance
2. Withdrawal
3. Taking larger amounts or over a longer period than was intended
4. A persistent desire or unsuccessful efforts to cut down or control substance use
5. A great deal of time is spent in activities necessary to obtain the substance, use the substance, or recover from its effects
6. Important social, occupational, or recreational activities are given up or reduced because of substance use
7. The substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem


What is tolerance?

Reduction in the effects of a given dose of a drug following repeated use


What is withdrawal?

Physiological and psychological symptoms that occur when drug use is stopped (usually opposite to effects of drug itself)


What do all drugs of abuse have in common?

They all activate mesolimbic dopamine system - reward pathways


What kind of reinforcement can drugs offer?

Positive - nice symptoms, euphoria etc – and...
Negative - reduction in anxiety, reduction in withdrawal symptoms


How can negative reinforcement interact with withdrawal to encourage drug use?

A person might begin to drink to relieve anxiety, say, then feel withdrawal symptoms, which are usually opposite of effects of drug (i.e. anxiety) and drink to relieve withdrawal-induced anxiety


What does Outcome Devaluation Task measure?

Difference between goal-oriented and habitual behaviours


How can behaviour shift from goal-oriented to habitual?

Over repeated trials, response to get desired substance is so often reinforced that stimulus-response conditioning occurs (eg. in bar, drink beer)


How does Outcome Devaluation Task work?

Animal is sated on substance (food, alcohol), then measured if will press lever it's been conditioned to press in order to receive same substance (habitual response) or another lever to receive a new substance (goal-oriented response).


How sensitive to alcohol devaluation were rats in Corbit et al. 2012?

After one week of training, animals pre-fed alcohol, reduced lever pressing for alcohol; after four weeks, trend upwards but not significant; after eight weeks, no sensitivity to devaluation of alcohol. After eight weeks - see a lever, push it - not reevaluating value of outcome, just automatic behaviour


What are the three phases of the Pavlovian-Instrumental Transfer paradigm?

1. Animals learn association between a stimulus and reward delivery (Pavlovian conditioning). Stimulus becomes cue for reward.
2. Trained to perform an instrumental response to get reward
3. Examine effect of reward-related cues on responding. Expected that cue enhances responding


What general principle does the Pavlovian Instrumental Paradigm illustrate?

That reward-related cues increase responding to get reward. Environmental stimuli can trigger reward-seeking behaviour – and their ability to do so increases with training


What two related shifts happen in drug-related behaviour by the eight-week mark?

Behaviour shifts from being sensitive to devaluation and reward value to being automatic - determined by environmental cues


How can drug-related stimuli contribute to relapse?

Because the user has been conditioned to seek the drug when these stimuli are presented


How does reinstatement work?

Reward-seeking behaviours that have been extinguished can be reinstated upon presentation of cue associated with the reward - environmental cue, stress etc.


How effective is extinction?

It doesn't entirely erase association. Evidence for this is provided by robust reinstatement effects. Neurally, perhaps, neurons already wired


How do we know which parts of brain are involved in reinstatement effect?

If prefrontal cortex and VTA are inhibited by a GABA agonist, a priming dose of cocaine does not produce a reinstatement effect


How can increasing neural plasticity help avoid reinstatement after extinction?

Chemically improving cognitive performance - with ADHD drug atomoxetine - during learning of extinction reduces reinstatement effect. Improves retention of learning.


Which drugs of abuse modify dopamine?

All of them


How are DA receptors in the striatum affected in alcoholics?

There are less D2 receptors


How are DA transporters in the striatum affected in methamphetamine addicts?

Less DA transporters, almost as few as Parkinson's patient


How does cocaine use affect brain activation in presence of natural rewards?

Less activation of various brain areas – cerebellum, orbitofrontal and prefrontal cortex, occipital cortex and thalamus - when presented with natural rewards such as food


How does chronic cocaine use appear to affect the brain? And what does this imply?

Decreased volume of grey matter in prefrontal cortex. Addicts less able to control behaviour


How does activation of prefrontal cortex correlate with progressive cocaine use?

Strong negative correlation – more cocaine taken each week, less activation of prefrontal cortex


What are three changes in the brains of chronic drug users?

1. DA receptors are downregulated
2. Response to natural rewards is blunted
3. Inhibitory brain areas, such as prefrontal cortex, are less active (although this may not be an effect of drugs - addicts may just have smaller PFCs to begin with)


What behavioural therapies exist for drug addiction?

Exposure therapy (extinction) - seems to work for alcohol

Stimulus control (avoid risky situations)
- effective, but most limiting on lifestyle

Contingency management interventions - giving positive reinforcement (eg. token system) for adherence to treatment plan


Name some harm reduction strategies for drug addicts

Replacement therapies - nicotine patches; methadone


How does alcohol aversion drug disulfiram (antabuse) work?

Blocks enzyme alcohol dehydrogenase, which converts acetaldehyde to acetate. Acetaldehyde builds up, causes vasodilation (widening of blood vessels), headaches, hypotension (low blood pressure), nausea and vomiting. Great, but compliance issues. Depot version.


What kind of replacement therapies are there?

Full agonists - methadone, nicotine patches

Partial agonists - drugs that bind to receptor but stimulate them weakly, and also block ability of natural NT to stimulate receptor Eg. buprenorphine for opiates, aripiprazole for stimulants


What happens if you take cocaine on partial DA agonist aripiprazole?

If you take cocaine on aripiprizole, it won't take effect as D2 receptors already occupied. Reinforcing effect of cocaine is minimized and reinstatement of habit less likely


What accounts for varying ability to handle alcohol?

Varying natural levels of alcohol dehydrogenase enzyme


What opiate antagonist can be used for alcoholism?

Naltrexone - blocks opiate receptors. Decreases total number of drinks per week in alcoholics, but not by that much from average of 32 to 24 - doesn't decrease to level of social drinkers (4 per week). Also decreases alcohol craving to same degree.


What level of abstinence is considered a good result for treatment program?

30% of abstinence after one year


What is LTP?

A long lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously