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40 Cards in this Set

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What is the physical reward pathway?
VTA --> nucleus accumben + prefrontal cortex
What type of neurons are the key players in the reward pathway?
dopaminergic neurons
What do abused substances have in common?
Increase the release of DA from the nucleus accumbens
What is the basal release?
% of compound which is released normally (when no drug present) this is 100%
What did the mouse model prove about the D2 receptor?
It is involved in the reward pathway but not with withdrawal symptoms
Main cause of receptor down regulation?
Increase stimulation of the receptor so receptor internalisation occurs/decrease in receptor expression may also lead to desensitisation
Main cause of receptor up regulation?
Under stimulation (eg due to antagonism) may also lead to sensitisation
What does receptor desensitisation refer to?
Uncoupling of 2nd messenger
When heroin passes the BBB what is it converted to?
Morphine
MOA of morphine in reward pathway?
Binds to MOP and inhibits release of GABA (by decreasing Ca influx) thus reducing inhibitory effects of GABA --> rush of DA release
Describe cocaine MOA
- Binds to DAT
- Prevents the degradation of DA by MAO
Why does combining heroin and morphine result in intense dopamine activation?
They act on different pathways
What is substitution therapy and give example
Where the abused substance is replaced by a less harmful compound eg. methadone (subtitutes morpine binds to MOP but no euphoria)
What is the active agent in tobacco?
Nicotine
Does nicotine stimulate the reward pathway?
Yes (via nAchRs in the brain)
In low doses nicotine has what kind of effects?
Stimulatory
In high doses nicotine has what kind of effects?
relaxing
Nictotine replacement strategy is as effective as...
placebo (25% success)
Name a nicotine replacement drug
Buproprion
What are 2 treatment methods of treating a nicotine addict?
- Nicotine replacement therapy (path, gum etc)
- Buproprion
How does buproprion take effect?
Weakly blocks DATs in the nucleu saccumbens
What is the first priority after someone has OD on drugs?
Pulmonary and cardiovascualr support
What are the difference of withdrawing from long and short acting drugs?
- Long acting drugs take longer to withdraw from but less withdrawal symptoms
- Short acting drugs are faster to withdraw from but stronger symptoms
What is precipitated withdrawal?
Patient is given an antagonist to the drug, very fast withdrawal BUT severe symptoms and high chance of relapse
What are some effects of withdrawal?
anxiety, dysphoria, irratibilty. tachycardia, restlessness
What enzyme does morphine inhibit?
Adenylyl cyclase
How does the brain readjust to the fact that morphine inhibits adenylyl cyclase?
Increases adenyly cyclase expression so that enough cAMP can be produced
What happens to adenylyl cyclase production after addict comes off morphine?
[Adenylyl cyclase] and [cAMP] very high so expression of adenylyl cyclase is reduced
Once withdrawal is successfully completed what is next?
Behavioural therapy
Describe the metabolism of alcohol
Alcohol --> acetaldehyde (by Alcohol dehydrogenase and NAD+) --> Acetic acid (by aldehyde dehydrogenase)
What is aversion therapy?
When taking drug gives bad feelings... dont like dont do!
Example of aversion therapy with ethanol
disulfiram - inhibits metabolism of alocohol leads to tachcardia, flushing, hyperventilation
What enzyme is often missing in asians?
aldehyde dehydrogenase
Methanol is metabolised to what? An d if consumed what can this cause?
Formate - blindness
reversed by giving ethanol (high affinity to the enzymes)
What is the overall effect of ethanol on the CNS?
CNS depression
List the effects of ethanol on CNS
- Enhances GABA inhibition
- Inhibition of NMDA, kainate receptors
- Inhibition of opening of Ca channels
- Increase of DA release in n. accumbens
Alcohol tolerance does what to GABAa and Ca channel and glutamate receptors receptor density?
Decreases GABAa, increase the others
What group does caffeine, theophylline adn theobromine come from?
xanthides
What are xanthides?
CNS stimulants
Caffeine is an antagonist of what at A2a receptor?
Adenosine