Neurobiology of substance misuse and addiction Flashcards
What is the ICD 11 criteria for harmful substance use?
A pattern of use that has caused harm to a patient or others through altered behaviour.
Harm to health occurs due to:
1) Behaviour related to intoxication
2) Direct or secondary toxic effects on body organs and systems
3) A harmful route of administration.
What is ICD 11 for dependence syndrome?
2 of the following:
- Impaired control over substance use
- Substance use becomes increasing priority
- Physiological features manifested by tolerance, withdrawal symptoms, repeated use to prevent withdrawal.
What is an issue when using the word ‘dependent’.
People can misinterpret dependence as a physiological dependence as seen in opioids. It is actually a label for compulsive, out of control drug use.
Just because something causes withdrawal symptoms does not make it addictive. Addiction is LACK OF CONTROL.
Where in the brain are dopamine rewards associated?
Ventral striatum/ Nucleus accumbens.
Mesolimbic pathway^
Substances of abuse increase these dopamine levels.
How does cocaine and amphetamine modulate dopamine action?
How do other drugs act (opiates, alcohol, nicotine)?
Cocaine blocks DA reuptake by blocking transporter.
Amphetamine blocks reuptake by blocking transporter, and enhances dopamine release.
Increase dopamine neuron firing in VTA. Other method, so takes longer for reward.
What happens to the dopamine system in addiction?
Brain gets depleted in dopamine and DA function is reduced. (Less D2 receptors)
Associated with irritability, low mood and associated with poor outcomes.
How do you image the DRD2 family?
Includes DRD 2,3,4.
D3 is in the limbic system- important in addiction.
11C-PHNO:
Agonist
DRD3 preferring
11C Raclopride:
Antagonist
DRD2>DRD3
What was found regarding the amount of DRD3 receptors in substance misuse disorders?
Alcohol: Higher DRD3 seen only in hypothalamus.
Cocaine and cannabis users showed higher D3 receptor levels, although dopamine levels were lower.
Correlations implicated D3 receptor levels in impulsiveness and risky decision making.
Which regions were activated by alcohol cues in alcoholics?
Ventral striatum
Anterior cingulate
Ventromedial prefrontal cortex.
What is GABA function in the VTA?
It is a break on dopaminergic cell firing. GABA-B receptor. Agonists can improve abstinence.
How does the opiate system modulate the GABA break?
u-opiate receptor is inhibitory. GABA neuron is shut down when activated, causing increased DA firing.
Naltrexone blocks u-opiate receptor, restoring GABA ‘break’
What is the significance of opioid receptor levels and dependence?
Alcoholics seem to have more opiate receptors compared to controls. (The more receptors they had, the more difficulty they had with craving)
Same was seen in Cocaine and opioids.
Therefore, the opiate system has a fundamental role in addiction.
What was the finding in a newer study?
There was no difference in mu opiate receptors in abstinent alcoholism compared with healthy controls.
Opioid release (endorphins) was much lower in alcohol dependent patients than healthy controls. (Amphetamine induced)
Why were the two contrasting studies different?
Length of abstinence- in Annes study, they were abstinent for months -years compared to day/weeks.
Annes study scanned ‘successful’ recovered/recovering alcoholics.
