engleski

Self-administration of cocaine and methamphetamine in Drosophila melanogaster

Addictive drug self-administration in used on laboratory animals because it models some aspects of addiction and drug consumption can be easily quantified. Drosophila preferentially consumes ethanol–containing liquid, but it could be the consequence of the evolution of Drosophila behavior that was shaped by fermenting food that contains ethanol. It is not known if psychostimulants, such as cocaine and methamphetamine, bitter compounds with no nutritional relevance for Drosophila, can induce preferential consumption. To test if flies will voluntarily self- administer psychostimulants we used the two- choice Capillary Feeder (CAFE) assay, where flies can choose between capillaries containing sweet liquid with or without addition of a psychostimulant. Preference Index (PI) is calculated based on the amount of food consumed each day for several days. In spite of the inherently aversive taste of bitter compounds, PI for both psychostimulants is positive from the first day of exposure, and on average flies show significantly higher PI for methamphetamine. Over the course of 4 days PI for cocaine increases and stays positive, while PI for methamphetamine decreases and becomes negative (aversive). Depending on the concentration, flies consume cocaine-containing food until the lethal outcome, suggesting the loss of behavioral flexibility. This is further supported by the cue-dependent consumption, because changing the location of drug containing capillaries every day or limiting cues leads to smaller PI. In order to obtain cocaine flies overcome addition of further bitter taste, quinine, indicating high motivation for consumption. To further validate our method we are characterizing responses of flies mutant for genes involved in preferential drug consumption in mammals. Above data suggests that Drosophila can develop preferential consumption for nutritionally irrelevant substance. Consumption of cocaine leads to behavioral changes that are commonly observed in mammals, such as loss of behavioral flexibility. Thus, Drosophila can be used as a tool in dissecting neural mechanisms underlying drug-seeking behavior and identification of new genes involved in development of addiction.

self-administration, psychostimulants, Drosophila melanogaster, preferential consumption

nije evidentirano