Effects of adrenergic agents on locomotor behavior and reproductive development inDrosophila

Abstract

Inhibition of tyrosine hydroxylase, the rate‐limiting enzyme in catecholamine biosynthesis, by α‐methyl‐p‐tyrosine (αMT) at media concentrations of 0.3–3.0 mM, markedly inhibited (>90%) fly reproduction and development as evidenced by progeny count. Under these conditions adult spontaneous locomotor activity (SMA) was also dose‐dependently reduced. However, no significant effects on behavior were observed at 0.3 mM. The behavioral effects of αMT were prevented by coadministration of L‐DOPA. Similar effects on behavior and development were produced by reserpine at doses of 0.1–1.0 mM. The higher doses affected behavior, but no behavioral effects occurred at 0.1 mM. Rescue from the effects of reserpine was also achieved with L‐DOPA. Treatment at 1 mM with the mammalian catecholamine receptor blockers propranolol (β1β2), raclopride (D2), SK&F 83566 (D1), prazosin (α1), and rauwolscine (α2) did not affect behavior. The two α adrenoceptor inhibitors, however, markedly decreased fly development. These results suggest that the receptor mechanisms mediating the effects of catecholamines on behavior and development are different. The locomotor behavior of adult progeny of parents treated with the lowest doses of αMT and reserpine described above was markedly suppressed by these drug treatments. This result indicates an increased sensitivity of the progeny to compounds which share the ability to deplete tissue catecholamines. Thus, alterations in catecholamine function during development may have behavioral consequences in surviving organisms. Drug Dev. Res. 50:142–146, 2000. © 2000 Wiley‐Liss, Inc.

RNAi-based screen for pigmentation in Drosophila melanogaster reveals regulators of brain dopamine and sleep

“…To systematically test if changes in pigmentation genes affect dopamine as theorized in the field, we characterized loss-of-function alleles of genes involved in dopamine metabolism (Figure 1A) for pigmentation phenotypes and dopamine levels in the head and brain. The enzymes required for dopamine synthesis, TH and Ddc, are essential for survival (Pendleton et al 2002;Wright et al 1976). Thus, we took advantage of established RNAi lines (Ni et al 2009;Pan et al 2022;Riemensperger et al 2013) and UAS/GAL4 system (Brand and Perrimon 1993) to examine their effects.…”

“…In addition to classifying neurological consequences in homologous human genes, we directly assessed neurological consequences in the fly. Since dopamine is known to regulate locomotion and sleep (Riemensperger et al 2011;Pendleton et al 2002), we screened for locomotion and sleep defects using the Drosophila Activity Monitor (DAM; Chiu et al 2010). We tested 274 RNAi lines from the NIG, TRiP, and VDRC RNAi collections (Dietzl et al 2007;Ni et al 2011;Vissers et al 2016) corresponding to 152 genes that showed consistent pigmentation defects.…”

RNAi-based screen for pigmentation in Drosophila melanogaster reveals regulators of brain dopamine and sleep

“…To systematically test if changes in pigmentation genes affect dopamine as theorized in the field, we characterized loss-of-function alleles of genes involved in dopamine metabolism (Figure 1A) for pigmentation phenotypes and dopamine levels in the head and brain. The enzymes required for dopamine synthesis, TH and Ddc, are essential for survival (Pendleton et al 2002;Wright et al 1976). Thus, we took advantage of established RNAi lines (Ni et al 2009;Pan et al 2022;Riemensperger et al 2013) and UAS/GAL4 system (Brand and Perrimon 1993) to examine their effects.…”

“…In addition to classifying neurological consequences in homologous human genes, we directly assessed neurological consequences in the fly. Since dopamine is known to regulate locomotion and sleep (Riemensperger et al 2011;Pendleton et al 2002), we screened for locomotion and sleep defects using the Drosophila Activity Monitor (DAM; Chiu et al 2010). We tested 274 RNAi lines from the NIG, TRiP, and VDRC RNAi collections (Dietzl et al 2007;Ni et al 2011;Vissers et al 2016) corresponding to 152 genes that showed consistent pigmentation defects.…”

Dopamine Dynamics and Signaling in <i>Drosophila</i>: An Overview of Genes, Drugs and Behavioral Paradigms

“…Supporting this, direct application of DA or DA agonists on an exposed nerve cord can stimulate stereotypical grooming behavior, whereas application of DA antagonists leads to akinesia [128]. In addition, subsequent studies using genetic or pharmacological manipulations to facilitate or inhibit DA secretion and signaling also show increased or decreased locomotion, respectively [28, 55, 76,77,78, 87, 110, 131]. Increases in DA reuptake by manipulation of DAT activity or treatment with cocaine are also in agreement with these studies [17, 58, 108, 110].…”

RNAi-based screen for pigmentation in Drosophila melanogaster reveals regulators of brain dopamine and sleep

“…To systematically test if changes in pigmentation genes affect dopamine as theorized in the field, we characterized loss-of-function alleles of genes involved in dopamine metabolism (Figure 1A) for pigmentation phenotypes and dopamine levels in the head and brain. The enzymes required for dopamine synthesis, TH and Ddc, are essential for survival (Pendleton et al 2002;Wright et al 1976). Thus, we took advantage of established RNAi lines (Ni et al 2009;Pan et al 2022;Riemensperger et al 2013) and UAS/GAL4 system (Brand and Perrimon 1993) to examine their effects.…”

“…In addition to classifying neurological consequences in homologous human genes, we directly assessed neurological consequences in the fly. Since dopamine is known to regulate locomotion and sleep (Riemensperger et al 2011;Pendleton et al 2002), we screened for locomotion and sleep defects using the Drosophila Activity Monitor (DAM; Chiu et al 2010). We tested 274 RNAi lines from the NIG, TRiP, and VDRC RNAi collections (Dietzl et al 2007;Ni et al 2011;Vissers et al 2016) corresponding to 152 genes that showed consistent pigmentation defects.…”

Dopamine Dynamics and Signaling in <i>Drosophila</i>: An Overview of Genes, Drugs and Behavioral Paradigms

“…Supporting this, direct application of DA or DA agonists on an exposed nerve cord can stimulate stereotypical grooming behavior, whereas application of DA antagonists leads to akinesia [128]. In addition, subsequent studies using genetic or pharmacological manipulations to facilitate or inhibit DA secretion and signaling also show increased or decreased locomotion, respectively [28, 55, 76,77,78, 87, 110, 131]. Increases in DA reuptake by manipulation of DAT activity or treatment with cocaine are also in agreement with these studies [17, 58, 108, 110].…”

RNAi-based screen for pigmentation in Drosophila melanogaster reveals regulators of brain dopamine and sleep

“…To systematically test if changes in pigmentation genes affect dopamine as theorized in the field, we characterized loss-of-function alleles of genes involved in dopamine metabolism (Figure 1A) for pigmentation phenotypes and dopamine levels in the head and brain. The enzymes required for dopamine synthesis, TH and Ddc, are essential for survival (Pendleton et al 2002;Wright et al 1976). Thus, we took advantage of established RNAi lines (Ni et al 2009;Pan et al 2022;Riemensperger et al 2013) and UAS/GAL4 system (Brand and Perrimon 1993) to examine their effects.…”

“…In addition to classifying neurological consequences in homologous human genes, we directly assessed neurological consequences in the fly. Since dopamine is known to regulate locomotion and sleep (Riemensperger et al 2011;Pendleton et al 2002), we screened for locomotion and sleep defects using the Drosophila Activity Monitor (DAM; Chiu et al 2010). We tested 274 RNAi lines from the NIG, TRiP, and VDRC RNAi collections (Dietzl et al 2007;Ni et al 2011;Vissers et al 2016) corresponding to 152 genes that showed consistent pigmentation defects.…”

Dopamine Dynamics and Signaling in <i>Drosophila</i>: An Overview of Genes, Drugs and Behavioral Paradigms

“…Supporting this, direct application of DA or DA agonists on an exposed nerve cord can stimulate stereotypical grooming behavior, whereas application of DA antagonists leads to akinesia [128]. In addition, subsequent studies using genetic or pharmacological manipulations to facilitate or inhibit DA secretion and signaling also show increased or decreased locomotion, respectively [28, 55, 76,77,78, 87, 110, 131]. Increases in DA reuptake by manipulation of DAT activity or treatment with cocaine are also in agreement with these studies [17, 58, 108, 110].…”