1 Substance Misuse and Harm Reduction. Novel addiction therapy approaches

What is Psychological dependence?

Craving, compulsive drug use, loss of control, ‘addiction’

What is Physical dependence?

When stopping a drug causes a withdrawal syndrome

What is tolerance?

When continued use of a drug results in the need for increasing doses for equivalent effect

What is the mesolimbic pathway?

• Cell bodies in ventral tegmental areas and axons in to Nucleus accumbens

• Reward pathway → Increase of dopamine release

Which are the 2 drugs abuse that do not increase dopamine

diazepam → is self administered
LSD

What does a decrease in dopamine cause?

dysphoria

How do cocaine and amphetamines cause increase of dopamine?

Dopamine signal terminated by proteins in nerve terminal
Block uptake of these proteins
Amphetamines cause dopamine release

How do opioids cause increase of dopamine?

act on m-opioid receptors on GABAergic neurones.
Cause disinhibition of DA neurones in VTA
More GABA means less dopamine MOR receptors inhibit release of GABA → excitation of dopamine neuron

What is GABA?

GABA main inhibitory → Neurotransmitter
Gi/o coupled

How do ethanol cause increase of dopamine?

acts directly on DA neurones in VTA. Decreases AHP, increases firing rate
blocks the K channel → the hyperpolarisation is shorter → allowing action potentials can fire more quickly and allows increased release of dopamine

What other things can ethanol do on the brain at different doses?

• Decreases After-Hyperpolarization (AHP)

• GABAA allosteric modulator

• NMDA receptor antagonist

• Calcium channel antagonist

Effective dose very high

How do nicotine cause increase of dopamine?

• acts on nicotinic acetylcholine receptors on DA neurones in VTA. Increases firing rate

• Ligand gate ion channels

How do cannabis cause increase of dopamine?

• THC: acts on cannabinoid receptors on GABAergic neurones.

• CB1 receptor → works similar to MOR

• Gi → Go coupled → inhibit GABA release

Why do certain stimuli need to be reinforced?

• certain things we need to do to stay alive

  • The euphoric reward for doing it

What is most important in Gi/o in nerve terminals/synapses?

closing a Ca2+ channels

What is most important in Gi/o in muscle?

andenylase cyclase inhibition

Why does inhaling drugs get a bigger subjective feeling of reward?

• Neurons → notice a change in neurotransmitter bigger the change the more the notice

  • faster release → more rewarding

Why can crack cocaine be smoked?

Cocaine hydrochloride turn into free-base (crack) vaporise at around 100degrees C, so can smoke it

Do you get withdrawal from cocaine?

No
But you do from crack

How does nicotine patches and methadone work?

Get roughly same blood levels → however reduces the rise in blood levels and then brain allows people to ween of delivering high volumes → but maintaining levels to stop physical withdrawal