Drug addiction Flashcards
How is the reward pathway involved in addiction?
It reinforces the activity that caused activation of the pathway e.g. sex, food when hungry
How do amphetamines increase dopamine levels?
Directly stimulate transmission of dopamine
How does nicotine increase dopamine levels?
Stimulates dopamine neurons
How does cocaine increase dopamine levels?
Blocks the removal of dopamine from the synapse, so the brain receives constant messages of euphoria
How do alcohol, opioids and cannabis increase dopamine levels?
Suppress the action of GABA neurons and others that inhibit dopamine release
What is condition place preference?
- Establish a side preference in the subject
- Expose the subject to something pleasurable (e.g. a drug or food) when confined to one side
- Test which side the subject prefers
What is the difference between crack cocaine and cocaine HCL?
- Crack cocaine is free base of cocaine i.e. not water soluble so cannot inject or snort
- Cocaine HCL is water soluble so can be snorted or injected
What do most highly addictive substances have in common in terms of route of administration and onset?
Most addictive substances have a fast onset and rapid decay - this is usually achieved via snorting or IV administration
Where does cocaine block dopamine reuptake?
- Cocaine binds to DA transporter on the presynaptic terminal in the striatum (more specifically the nucleus accumbens)
- Cocaine blocks the transporter from dopamine uptake
How do amphetamines increase dopamine release in the nucleus accumbens?
- They mimic DA and get pumped into the presynaptic terminal into a vesicle, preventing DA from being pumped into the vesicle.
- Thus leading to high levels of DA outside the synapse
How does this diagram demonstrate why cocaine is more likely to become addictive than methamphetamine?
- Cocaine has a rapid uptake and rapid decay/clearance
- Methamphetamine has a rapid uptake and slow clearance
How does nicotine stimulate dopamine release?
- Through depolarisation of DA neurons.
- Nicotinic channels are non-selective cation channels.
- Calcium entry directly through receptor can supply enough calcium to trigger DA release
How is ethanol absorbed?
Rapidly (slowed by food), some metabolism in the gut, but most distributes to all tissues (inc. placenta –> FAS)
How is ethanol metabolised?
- Via alcohol dehydrogenase (ADH) in the liver and gut.
- Microsomal ethanol-oxidising enzyme (p450) kicks in above 0.1% blood ethanol i.e. when drunk
What are the 2 kinds of tolerance?
- Metabolic (pharmacokinetic) tolerance
- Functional (pharmacodynamic) tolerance
How are drugs like disulfram and antabuse supposed to stop alcoholics from wanting to drink?
They inhibit acetaldehyde dehydrogenase from converting acetaldehyde into acetic acid which causes nausea and vomiting (hangover symptoms)
How does naltrexone work in alcohol and opioid dependence?
- Blocks opioid receptors and blocks the effects of endogenous opioid peptides like dynorphin.
- Dynorphin triggers drug seeking behaviours and decreases DA signalling in the nucleus accumbens
- Thus naltrexone reduces the rewarding effects of alcohol and opioids
How is acamprosate proposed to work as an anti-craving medication in alcoholism?
- It is an anti-epileptic medication that may work by compensating for the increased excitability in the brains of alcoholics during withdrawal.
- Thought to increase the activity of GABAa receptors while inhibiting glutamate receptor activity
When would SSRIs be helpful in patients with alcoholism?
If they had co-morbid depression
How is nalmefene proposed to work as an anti-craving medication in alcoholism?
- Reduces craving presumably by antagonising the effects of endogenous opioid peptides.
- Reduces the rewarding effects of alcohol.
- Has a longer half-life than naltrexone, greater oral bioavailability and does not induce liver toxicity.
What is the allostasis theory of addiction?
- Starts with impulsive reward-seeking (drug experimentation)
- With repeated exposure to the drug, pleasure effects diminish.
- Thereafter compulsive drug use becomes dominant to avoid withdrawal.
- Withdrawal causes negative reinforcement - “I need the drug because I feel sick” whereas before it was positive reinforcement, “I need the drug because it feels good”
What are the 3 main stages of the addiction cycle?
- Binge/intoxication - positive reinforcement
- Withdrawal/ negative affect - negative reinforcement
- Preoccupation/anticipation - craving
