engleski

Locomotor sensitization modulates voluntary self-administration of methamphetamine in Drosophila melanogaster

As complexities of addictive behaviors cannot be fully captured in laboratory studies, scientists use simple addiction- associated phenotypes and measure them inlaboratory animals. Locomotor sensitization, characterized by an increased behavioralresponse to the same dose of the drug, has been extensively used to elucidate thegenetic basis and molecular mechanisms of neuronal plasticity. However, to whatextent it contributes to the development of addiction is not completely clear. Wetested if the development of locomotor sensitization to methamphetamine affectsvoluntary self- administration, and vice versa, in order to investigate how two drug-associated phenotypes influence one another. In our study, we used the geneticallytractable model organism, Drosophila melanogaster, and quantified locomotorsensitization and voluntary self- administration to methamphetamine using behavioraltests that were developed and adapted in our laboratory. We show that flies expressrobust locomotor sensitization to the second dose of volatilized methamphetamine, which significantly lowers preferential self- administration of methamphetamine.Naive flies preferentially self-administer food with methamphetamine over plainfood. Exposing flies to volatilized methamphetamine after voluntary self- administration abolishes locomotor sensitization. We tested period null (per01) mutantflies and showed that they do not develop locomotor sensitization, nor do they showpreferential self-administration of methamphetamine. Our results suggest that theremay be partially overlapping neural circuitry that regulates the expression oflocomotor sensitization and preferential self-administration to methamphetamineand that this circuitry requires a functional per gene.

Drosophila melanogaster, locomotor sensitization, methamphetamine preference, period gene, self-administration

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