Multiple roles for dopamine in Drosophila development.
Manipulation of dopamine levels by inhibition of tyrosine hydroxylase activity was accomplished in Drosophila melanogaster larval instars by feeding enzyme inhibitors for a 24-hr period. Behavioral assays performed immediately after treatment demonstrated that larval phototaxis, salt aversion, and heptanol preference were unaffected by reduced levels of dopamine. Within a few hours of treatment, the larvae ceased exploratory behavior and were unresponsive to external stimuli; these larvae eventually died. This behavior is strikingly similar to that displayed by dopamine-deficient transgenic mice. Treated larvae placed immediately onto normal food (to replenish dopamine levels) showed significant developmental delays and decreased fertility as adults. The lethality, developmental retardation, and decrease in fertility were reversed by addition of L-DOPA to inhibitor-containing food, suggesting that these effects were due solely to inhibition of tyrosine hydroxylation. Depletion of dopamine in newly eclosed females resulted in abnormally developed ovaries. These results suggest that the enzymatic function of tyrosine hydroxylase is vital and that reduced levels of dopamine result in akinesia and lethality, developmental retardation, and decreased fertility.
Neckameyer
W S
WS
Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, Missouri 63108, USA.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D004331:Drosophila melanogaster / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005298:Fertility / Q000187:drug effects / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D017403:In Situ Hybridization; D007814:Larva / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D008781:Methyltyrosines / Q000494:pharmacology; D051379:Mice; D007470:Monoiodotyrosine / Q000494:pharmacology; D010053:Ovary / Q000187:drug effects / Q000254:growth & development; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors / Q000235:genetics
D004791:Enzyme Inhibitors; D008781:Methyltyrosines; D012333:RNA, Messenger; C022260:alpha-methyltyrosine methyl ester; D014446:Tyrosine 3-Monooxygenase; D007470:Monoiodotyrosine; D004298:Dopamine