Drug addiction Flashcards
What is the worst drug of addiction in western society?
Alcohol
Where do drugs exert their effects?
On different receptors of the brain
What R do: - Opiates - Nicotine - Cannabis - Alcohol Effect??
Opiates - opiate R
Nicotine - ACh R
Cannabis - Cannaboid
Alcohol:
- SEVERAL different receptors
- Main ones being: GABA and NDMA
What do drugs of abuse act secondarily through?
Dopamine release from the mesolimbic ‘reward’ system
Where is DA released from in the MLR pathway?
FROM: Ventral Tegmental Area neurons
INTO: Frontal cortex and the nucleus accumbens
What is the nucleus accumbens involved in?
The REWARD circuit
What are natural rewards?
Food
Sex
Social interaction
What are learned rewards?
Positive reinforcement to drug addiction
Why are some people more likely to develop an addiction?
1) GENETICS
2) SOCIAL ENVIRONMENT
3) PERSONALITY/PERSONAL HISTORY
How does genetics influence drug addiction?
Determines sensitivity and development of tolerance
What is SENSITIVITY?
The INABILITY to tolerate the adverse effects of a drug (how much of a drug can be consumed before has an effect)
What is the DEVELOPMENT of TOLERANCE?
Reduction in sensitivity when a drug is REPEATEDLY used over time
(higher amount to achieve the same response)
How can SENSITIVITY and TOLERANCE be studied?
Model organisms - drosophila
Why are flies a good model?
FAST generation time
~50% of drosophila genes in humans
~75% of genes implicated in disease are present in drosophila
Simple but exhibit COMPLEX behaviours that can be used to IDENTIFY GENES on a whole genome level
There are mutant and transgenic flies for almost EVERY gene in the drosophila genome
What categories of genes are well suited to drosophila analysis? (5)
- Neurological diseases
- Cancer
- Developmental disorders
- Metabolic disorders
- Cardiovascular disease
Are flies a good model for drug addiction?
- Genes associated with alcohol addiction in humans (GABA, NMDA, dopamine)
- BUT, no OPIOD/CANNABINOID R in drosophila
Describe the study of flies with ethanol (booz-o-mat)
‘booz-o-mat’:
- Flies in chamber
- Humidified air (control) OR air with ethanol
- Record the behaviour of flies over time
Results:
- Flies move more ACTIVELY when ethanol is applied
- Over time - ethanol treatment causes the flies to fall over
Describe the locomotor velocity profile of flies with ethanol
What is important about this experiment?
BEHAVIOUR over time:
- Startle response (sharp increase and decrease again)
- Increase in locomotion
- Sedation
SAME effects at the same concentrations as in HUMANS
Why must different technique be used to determine the effects of ethanol on drosophila?
Because BEHAVIOUR is not good for HIGH-THROUGHPUT screening
Describe a second study of flies with ethanol (inebriometer)
- Tube with series of steps
Flies into chamber from the top:
- If sober/active –> crawl up the steps and stay in the chamber
- If drunk to a state of unconsciousness –> flies fall over and fall out of the tube
- Measure ELUTION time for flies