SUHRT - Novel addiction therapy approaches (L1)

Reward vs Reinforce

Reinforce: objective term - something is reinforcing when an animal will perform a behaviour in order to obtain that stimulus. ie. It is rewarding.

Reward: subjective term - A feeling of great happiness or well-being which is linked to euphoria

Psychological dependence, Physical dependence and Tolerance

Psychological dependence - Craving, compulsive drug use, loss of control, ‘addiction’

Physical dependence - When stopping a drug causes a withdrawal syndrome

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

Three main dopaminergic pathways in the brain

Nigrostriatal pathway - from substantia nigra to caudate which related to PD

Mesocortical pathway - originates in Ventral Tegmental area and related to schizophrenia

Mesolimbic pathway - related to addiction

k opioid receptor agonists vs m opioid receptor agonists

k = decrease in dopamine release which means they’re dysphoric

m = opposite

Which drugs cause an increase in dopamine in the nucleus accumbens?

Diazepam

LSD - hallucinogenic and not really addictive

How does cocaine and amphetamines increase DA levels in NAcc?

Usually:

• GABA binds to the dopaminergic neurone causing AP

• AP causes dopamine to be released in the nerve terminals

• Activates receptors

• Taken back up into the nerve terminal and away from the receptors so they are no longer activated

With the psychostimulants:

• Inhibits the reuptake of dopamine so it hangs around longer and the receptor continues to be activated for longer

How does opiates increase DA levels in NAcc?

• opiates act on the m-opioid receptors on gabaminergic neurones

• binds to Gi/o receptor causing decrease of CA++ in and increase of K+ out

• this reduces the AMP → cAMP→ PKA pathway

• K+ causes hyperpolarisation and Ca++ stops NT release

• This inhibits the GABA neurone so the dopamine stays longer cause the “brakes are stopped”

How does ethanol increase DA levels in NAcc?

“dirty drug”

Decreases After-Hyperpolarization (AHP) - potassium channel blocker so more AP fired

How does Nicotine increase DA levels in NAcc?

acts on nicotinic acetylcholine receptors on DA neurones in VTA

causes the ligand gated ion channel to open

most permeable to Na so it enters and depolarise so more likely to fire AP

this means more release of dopamine at the nerve terminals

How does THC increase DA levels in NAcc?

THC binds to CB1 receptors on GABA

same thing as opioid in terms of the Gi/o coupled receptors

Routes of administration for drugs

Inhaled - fastest so feels more rewarding and euphoragenic cause there is a higher rate of change

Oral = longest

Crack cocaine

Can become a vapour at just over 100C so much more addictive

Heroine vs Morphine

Herione = diacetyl morphine also referred to as diamorphine

Acetyl groups instead of C-OOH its C-OOCMe

The acetyle allows it to cross the BBB much faster so more addictive and higher abuse potential