engleski

Drosophila melanogaster as model for studying drug addiction – introduction of self- administration paradigm: preferential consumption of cocaine in Drosophila melanogaste

Drug addiction is defined as a chronic, relapsing brain disease that is characterized by compulsive drug seeking and use, despite harmful consequences. The self-administration paradigm serves as a behavioral phenotype that can be measured in laboratory animals and models features of addiction. Drosophila preferentially consumes ethanol–containing food, however it is not known if the same is true for psychostimulants, cocaine and methamphetamine. To test if flies will voluntarily self- administer psychostimulants we used the two- choice Capillary Feeder (CAFE) assay, where flies can choose between capillaries with drug- food or a non-drug food. Preference Index is calculated based on the amount of food consumed each day for several days. We show that PI for cocaine is positive from the first day and increases over consecutive days, in spite of inherently bitter taste of cocaine. Depending on the concentration, flies can consume cocaine-containing food in spite of negative consequences (lethality), suggesting the loss of behavioral flexibility. After period of abstinence from cocaine-containing food flies rapidly return to the same or greater PI, suggesting relapse-like effect. Flies overcame aversive stimulus (bitter tasting quinine) in order to obtain cocaine, and positive PI from the first day of exposure further supports that. PI for methamphetamine on day one was significantly higher than for cocaine, but then decreased over consecutive days, suggesting mechanistic difference of action on brain areas that regulate preferential consumption. Based on the above data we propose that self- administration phenotype can be very useful in dissecting neural mechanisms underlying drug- seeking behavior. In particular, Drosophila can be used for identification of new genes involved in development of addiction, which can then advance further mechanistic studies in mammals.

rewarding effect, psychostimulants, Drosophila melanogaster, self-administration

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