Screening Antimalarial Drugs for Modulation of Aggressive Behaviour in Drosophila melanogaster

Namirimu Regina Mary

School of Pharmacy, Kampala International University, Uganda

ABSTRACT

Aggressive behavior is crucial to survival and reproduction in organisms and this can be affected by environmental factors. Antimalarials are commonly used in medical practice, and it’s possible that they would interact with modulators of aggression to influence behavior since some have been shown to cause neuro-damage. This study evaluated common antimalarial drugs for the modulation of aggressive behavior in Drosophila melanogaster model. Drosophila melanogaster specie (W118) was used in this study. Flies were divided into male and female and experiments were conducted on adult, middle, and juvenile age groups. Flies were exposed to chloroquine (0.0025 mg/ml), quinine (0.000135 mg/ml), Fansidar (0.0025 mg/ml), Artesunate (0.0003 mg/ml), and Artemether lumefantrine (0.0003 mg/ml). These were later on exposed to neurotransmitter modulators i.e. octopamine (stimulatory-clonidine (1 mg/ml); inhibitory-promethazine (0.00025 mg/ml), dopamine (stimulatory-L-dopa (0.001 mg/ml); inhibitor-haloperidol (0.0001 mg/ml), serotonin (stimulatory-fluoxetine (0.0002 mg/ml), inhibitory-cyproheptadine (0.00004 mg/ml). Data was recorded in triplicate and analyzed in MS Excel. Information was presented in mean± SEM and significance at 95% was considered. The study showed that Artesunate had the highest effects of aggression in male Drosophila melanogaster flies while Quinine and Chloroquine were associated with low effects and Artemether lumefantrine was associated with low levels of aggression in female flies. These observations would have been due to their interaction with neurotransmitter release which is essential for aggressive behavior. Fansidar and Artemether-lumefantrine acted synergistic to octopaminergic stimulation in both males and females respectively. Artesunate antagonized actions of promethazine by leading to increased aggression, especially in male flies. Fansidar and Artemether-lumefantrine acted synergistically to dopaminergic stimulation while Artesunate antagonized dopaminergic inhibition, showing that it plays a crucial role in aggression. Serotonin leads to decreased aggression and Fansidar showed antagonist activity in males while in females this was in Artemether Lumefantrine. Artesunate showed strong inhibitory activity on serotonin release, thus leading to increased aggression. In the age groups, aggression by Artesunate was highest in adult male and female flies and this raises major pharmaceutical concerns. In the juveniles, Fansidar and Artesunate showed significant aggression, thus showing implications in neural development. The molecular mechanism of actions of Artesunate and Fansidar on modulation of neurotransmitter release needs to be investigated further to gain clear insight.

Keywords: Aggressive behavior, Drosophila melanogaster, Antimalarial drugs, Neurotransmitters, Pharmacology

CITE AS: Namirimu Regina Mary (2024). Screening Antimalarial Drugs for Modulation of Aggressive Behaviour in Drosophila melanogaster. RESEARCH INVENTION JOURNAL OF BIOLOGICAL AND APPLIED SCIENCES 3(1):1-16.