Addiction and drugs of abuse Flashcards
What is addiction?
A progressive and often fatal behavioural syndrome characterized by compulsive drug seeking and consumption despite serious negative consequences.
Characterized by:
Overwhelming involvement with the use of a drug (compulsive use).
The securing of its supply (compulsive drug-seeking).
A high tendency to relapse after withdrawal.
What are the risk factors for addiction?
Heritability - genetic variation
Personality - not everyone who takes a drug once gets addicted to it.
Environment:
Peer pressure. Family environment (parental influence).
What is the reward pathway?
Also known as the mesimbolic pathway.
Mainly located in the limbic system and functions to monitor internal homeostasis, mediate memory, mediate learning and experience emotion.
Main structures include Includes the hypothalamus, amygdala, hippocampus, nucleus accumbens (NA), the ventral tegmental area (VTA), locus coeruleus and the prefrontal cortex.
What is the reward pathway stimulated by?
Natural - food, sex, drinks.
Behaviours - gambling.
Drugs - drugs of abuse (hyperactivity).
Diseases - psychosis, schizophrenia.
How is dopamine related to the reward pathway?
Dopamine is the primary neurotransmitter of the reward pathway.
All drugs of abuse increase dopamine levels in the brain reward pathway although they often act through separate mechanisms.
Drugs that are not abused have no effect on dopamine concentrations in the reward pathway.
What do addictive drugs do?
Increase activity of opioid and DA neurons.
Decrease activity of GABAergic interneurons.
How do drugs alter our brain and behaviour?
Acute reinforcement of the reward pathway.
Repeated drug use –> Compulsion to seek and take drugs.
Loss of control in limiting intake due to withdrawal symptoms.
Development of tolerance –> more drugs required to produce high tolerance.
What is the pathway on compulsion to seek and take the drug?
Natural rewards - release of DA.
DA binds to receptors on post synaptic neuron.
Reward and high.
DA transporter pumps DA back into the cell (cocaine prevents it).
DA levels in the synapse increased –> receiving neuron stimulated constantly - euphoria {alteration of brain circuits – natural rewards no longer produce high}.
Use of drug becomes obligatory.
What is the pathway on loss of control in limiting intake?
After cocaine use - DA levels fall below normal.
Low mood.
To alleviate - uses drug again.
What is the pathway on tolerance?
Chronic use of cocaine.
Continuous above normal levels of DA.
Reduction in no. of DA receptors.
Larger amount of drug needed to get same HIGH.
What are the mechanisms of action of drugs for opioid addiction: methadone, buprenorphine, naloxone, naltrexone and clonidine.
Methadone (μ-opioid receptor agonist -> replacement therapy).
Buprenorphine (partial μ-opioid receptor agonist -> replacement therapy).
Naloxone (short acting opioid receptor antagonist -> mainly used in overdose).
Naltrexone (long acting u-opioid receptor antagonist -> (used for withdrawal from opioids).
Clonidine (alpha2 adrenergic agonist acting presynaptically to reduce release of neurotransmitters such as noradrenaline).
What are the mechanisms of action of drugs for alcohol addiction: benzodiazepines, disulfiram, naltrexone, acamprostate and NAc neurons
Benzodiazepines (sedative used for withdrawal; targets GABAa receptors).
Disulfiram (inhibits aldehyde dehydrogenase, produced aversion to alcohol; hangover).
Naltrexone (selective u-opioid receptor antagonist).
Acamprosate (interact with neuronal NMDA receptors and calcium channels on NAc neurons -> restores normal glutamatergic transmission within the reward pathway).
What are the mechanisms of action of drugs for cocaine addiction: bromocriptine and amantadine?
No current treatment that is effective.
Bromocriptine and amantadine (dopamine agonists, experimental drugs that have shown promise as replacement therapy).
What are the stages of addiction?
Initiation. Experimentation. Regular Usage. Risky Usage. Dependence. Addiction. Crisis/Treatment.
