3 Substance Misuse and Harm Reduction. Novel addiction therapy approaches

How does the mesolimbic pathway work?

• Dopamine released in NA

  • Activates D1 receptors → largely feedback neurones (GS)

  • Project back into the ventral tegmental area and try to dampen down this circuit

  • Release dynorphin which causes the prolonged activation of kappa opioid receptors which causes the dysphoria

  • D2 receptors both at GPCR (Gi/Go)

  • Frontal cortex that allow the conscious perception of euphoria

  • D2 most important in modulating euphoria

Are some people predisposed to addiction?

• Drug has less effect on those who use cocaine

• Less receptors

• Possibly start off with less receptors

• Possible due to SNP

• Taking of some drugs can decrease receptors

How does a PET scan work?

• In vivo → works the same way as radio ligand binding]

• Red is radioactive ligands that bind to receptors in green

• Dopamine competes with the radioactive ligand

• End up with fewer receptors with the radio active ligand bound

• Neurone with fewer receptors

  • Fewer binding sites to fewer radioactive ligands bound to neurone

What happens if you put an animal in a no rewarding cage?

Decreases D2 levels and increases cocaine self-administration

What is the idea about low D2 receptors?

Environmental factors → low D2 receptors → low reward → enhanced liking of illicit drugs → enhanced drug taking → resulting in low D2 levels

What is Bupropion (zyban)?

• dopamine / noradrenaline reuptake inhibitor

• Might just work because it’s an antidepressant

might work better in people with lower D2 levels

What is Bromocriptine?

D2 partial agonist
might work better in people with lower D2 levels

What is addiction?

• a learned process

• Memory formation is thought to occur because of synaptic plasticity, particularly at glutamatergic synapses

What happens when Inhibiting synaptic plasticity?

inhibits memory formation) inhibits conditioning learning

How can you treat people that are already addicts?

interfering with reconsolidation

by using synaptic plasticity inhibition

What would synaptic plasticity inhibition involve?

involve re-exposure to cues, along with agents that interfere with memory formation

Current treatments for drug use?

Replacement → OST/Nicotine
Aversion
Antagonists
Bupropion/bromocriptine

Future treatments for drug use?

Antibodies
Stress hormone antagonists
KOR antagonists
Agents that affect memory