The trace amine tyramine is essential for sensitization to cocaine in Drosophila.
BACKGROUND
Sensitization to psychostimulant drugs of abuse is thought to be an important aspect of human addiction, yet how it develops is still unclear. The development of sensitization to cocaine in the fruit fly Drosophila melanogaster is strikingly similar to that observed in vertebrates. By taking advantage of the powerful genetic approaches that are possible in Drosophila, we are able to identify and characterize mutants that fail to develop sensitization.


RESULTS
We found that the Drosophila mutant inactive (iav) failed to become sensitized to cocaine. Mutant flies had reduced amounts of the trace amine tyramine in the brain because of reduced activity of the enzyme tyrosine decarboxylase (TDC), which converts tyrosine to tyramine. Furthermore, cocaine exposure induced TDC enzyme activity in a time-dependent manner that paralleled the development of behavioral sensitization. The sensitization failure of iav flies could be rescued by feeding the flies with tyramine; other biogenic amines or amine precursors did not have the same effect.


CONCLUSIONS
These results indicate an essential role for tyramine in cocaine sensitization in Drosophila.
McClung
C
C
Department of Biology, University of Virginia, Charlottesville, Virginia 22903, USA.
Hirsh
J
J
D000818:Animals; D001921:Brain / Q000201:enzymology; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000235:genetics; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009154:Mutation; D009655:Octopamine / Q000502:physiology; D013997:Time Factors; D014439:Tyramine / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism; D014445:Tyrosine Decarboxylase / Q000378:metabolism*
D018765:Dopamine Uptake Inhibitors; D009655:Octopamine; D014443:Tyrosine; D006899:Mixed Function Oxygenases; C023205:tyramine beta-hydroxylase; D014445:Tyrosine Decarboxylase; D003042:Cocaine; D014439:Tyramine