drosophila drug addiction

Question 1

what drugs are most harmful?

Answer 1

• alcohol (8400 alcohol related deaths in UK a year)

- cocaine and heroin

Question 2

why do drugs have diffferent primary effects?

Answer 2

• as they act on different receptors
  e.g. alcohol - GABA and NMDA
  cannabis - cannabinoid
  nictotine - AchR

Question 3

how do most drugs act secondarily?

Answer 3

• most drugs act secondarily through the dopiminergic and mesolimbic reward system

Question 4

what are the contributing factors to drug addiction

Answer 4

• genetic (tolerence development and sensitivity)
• social environment
• personality and personal history

Question 5

are drosphila a good model organism for drig addiction?

Answer 5

50% of drosophila genes in human
75% of disease associated genes in the drosophila

• dopamine, GABA and NMDA receptors in drosophila (good model for alcohol)
• no cannabinoid receptors (not a good model for cannabis)

-can induce mutations (radiation) and screen and understand genetic components of alcohol addiction but cannot measure environment and personality.

Question 6

what response to flies show to alcohol?

Answer 6

• on a boozo-mat with ethanol fumes
• show initial startle response, then increased locomotion followed by sedation
• similar to human response

Question 7

what is an inebriometer?

Answer 7

• chamber infused with ethanol fumes - flies fall out when too drunk - elution time measured
• sober flies stay in the chamber for longer

-flies irradiated to induce mutations - flies that stay in the longest and are eluted first are screened and genes identified

Question 8

what happens in the cheapdate mutant and why?

Answer 8

• alcohol sensitivity is reduced - fall out first
• cheapdate is an allele of amnesiac - activated Camp
• activity of camp pathway reduces sensitivty
• if cheapdate mutated - cannot activate camp - low levels of camp - high sensitivity

-flies are less sensitive to ethanol a second time (can develop a tolerance?

Question 9

what happens in hangover mutants and why?

Answer 9

• hangover mutants have decreased tolerence
• don’t uild up as much of a tolerance as WT flies
• hangover encodes a RNA binding protein which binds to DUNCE
• balance between hangover and dunce dtermines toleracne
• hangover links 2 CAMp dependent mechanisms
• DUNCE and hangover mutants have elevated CAMP levels
• CAMP reduces tolerence - hence tolerance is reduced in hangover and dunce mutants