Dopaminergic regulation of circadian locomotor activity and resistance to oxidative stress in Drosophila melanogaster

Dopamine (DA) is the sole neuroactive catecholamine in Drosophila melanogaster which regulates locomotor behavior along with various physiological and developmental functions. We monitored the impact of mutations in three key genes in DA regulation on circadian locomotor behavior and resistance to oxidative stress (OS) in D. melanogaster. Catecholamines up (Catsup) - a negative regulator of DA production acts on tyrosine hydroxylase (TH)-a rate limiting enzyme for DA synthesis. pale (ple) encodes TH and Punch (Pu) encodes GTP cyclohydrolase (GTPCH) important for synthesis of tetrahydrobiopterin (BH₄) necessary for TH activity. A mutant in the vesicular monoamine transporter (VMAT) a key transporter which helps in transport and packaging of DA in the vesicles of the DA neurons was also studied. Male flies of all mutants with isogenized controls (6-8 days old) were used to study circadian locomotor activity rhythms, longevity as well as resistance to OS induced by both hydrogen peroxide and Paraquat.  In general, most mutant flies exhibited rhythmic circadian locomotor activity. Catsup mutants were however significantly more hyperactive compared to ple, Pu and VMAT mutants. When DA synthesis pathway was affected, life span was impacted along with a differential response in antioxidant systems in response to OS. Taken together, we hypothesize that DA could have a significant role in regulation of response to OS independent of the circadian system. Further studies on the downstream targets of DA with special reference to OS will help clarify the precise molecular mechanism of DA function in organismal homeostasis.