Defining the preferential consumption of cocaine and methamphetamine in Drosophila melanogaster

Ovisnost je stanje u kojem organizam osjeća jaku psihičku ili fizičku potrebu za opojnom supstancom. Psihostimulativne droge, poput kokaina i metamfetamina, djeluju na centre u mozgu koji reguliraju procesuiranje nagrade. Nagrađujući utjecaj droga kao posljedicu ima povećanu privlačnost droge koja dovodi do ovisničkog ponašanja, a može se ispitivati na laboratorijskim životinjama kao preferencijalna konzumacija. Iako postoje mnogi eseji za mjerenje lokomotornih efekta kokaina i metamfetamina, platforma kojom bi se promatrao nagrađujući utjecaj psihostimuansa kod Drosophile melanogaster dosada nije bila razvijena. Cilj ovog diplomskog rada bio je modificirati Capillary Feeding (CAFE) esej prvotno osmišljen za ispitivanje ovisnosti o alkoholu i definirati karakteristike preferencijalne konzumacije kokaina i metamfetamina kod vinske mušice kao modelnog organizma za izučavanje ovisničkih ponašanja. Utvrdili smo kako mušice prilikom samoadministracije kokaina i metamfetamina razvijaju obrasce ovisničkog ponašanja primijećene u ljudi i modelima glodavaca. One aktivno biraju i preferiraju hranu s kokainom ili metamfetaminom unatoč gorkom okusu ovih psihostimulansa, te nastavljaju konzumaciju usprkos negativnim posljedicama i nakon deprivacije razvijaju ponašanja slična recidivu. Naši rezultati sugeriraju kako su u razvoju preferencijalne konzumacije na kokain uključeni produkti cycle gena, u preferenciji metamfetamina produkti period, Clock i cycle gena, te kako dopaminski transporter i receptor tip 1 nisu uključeni u razvoj preferencijalne konzumacije. Korištenje Drosophile u ispitivanjima samoadministracije omogućiti će daljnja istraživanja neuroloških mehanizama koji su u podlozi nagrađujućeg djelovanja psihostimulansa kako bi se u budućnosti dizajnirali farmakološki tretmani za spriječavanje ili liječenje ovisnosti.Addiction is a condition where organism feels a strong psychological or physical need for narcotic substance. Psychostimulative drugs, like cocaine and methamphetamine, affect neural mechanisms involved in the processing of rewards. Because of the rewarding effect of a drug, attraction for a drug leads to addictive behavior. This behavior can be investigated in laboratory animals as preferential consumption. Although there are many assays to measure locomotor effects of cocaine and methamphetamine, a way to measure rewarding influence of psychostimulants in Drosophila melanogaster has not yet been developed. The aim of this thesis was to define the characteristics of preferential consumption for cocaine and methamphetamine in fruit flies as a model organism to study addictive behaviors. In order to do that, we modified the Capillary Feeding (CAFE) essay initially designed to test alcohol dependence. We find that fruit flies willingly self-administrate cocaine and methamphetamine and develop patterns of addictive behavior similar to ones observed in humans and rodent models. Fruit flies actively choose and prefer food with cocaine or methamphetamine despite of bitter taste of these psychostimulants, they continue to consume drugs despite negative consequences and after deprivation develop behaviors similar to relapse. Our results suggest that the development of preferential consumption for cocaine depends on cycle gene products, that preference for methamphetamine involves period, Clock and cycle genes, and that dopamine transporter and dopamine receptor type 1 are not involved in the development of preferential consumption. The use of Drosophila in self-administration experiments will be useful in further research on neurological mechanisms of rewarding action of psychostimulants, with final goal of designing pharmacological treatments for prevention and treatment of addiction