Effects of adrenergic agents on locomotor behavior and reproductive development in Drosophila

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 (β 1 β 2 ), raclopride (D 2 ), SK&F 83566 (D 1 ), prazosin (α 1 ), and rauwolscine (α 2 ) 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.

Drosophila melanogaster as a genetic model system to study neurotransmitter transporters

“…Under standard fly culture conditions, loss of dVMAT is lethal, but reducing the density of the culture results in 100% viability, thus allowing behavioral assays. dVMAT mutants show a dramatic decrease in baseline larval locomotion (Simon et al, 2009), mirroring previously demonstrated effects of reserpine (Pendleton et al, 2000) . dVMAT mutants also show a reduced startle response, reduced male courtship (Simon et al, 2009) and increased sleep (Nall and Sehgal, 2013).…”

Overexpression of the Drosophila vesicular monoamine transporter increases motor activity and courtship but decreases the behavioral response to cocaine

“…51 We observe a similar decrease in locomotor activity (Figure 3a) and grooming (Figure 3b) in flies treated with reserpine, confirming that the storage of monoamines by DVMAT is required for motor behaviors in the adult fly. We also find that treatment of adult flies with reserpine decreases the number of adult progeny produced by wild-type flies at concentrations as low as 1 mM (Figure 3c), consistent with other reports similarly investigating the effects of this and other aminergic agents on fertility.…”

Drosophila Vesicular Monoamine Transporter Mutants Can Adapt to Reduced or Eliminated Vesicular Stores of Dopamine and Serotonin

“…In contrast, null dVMAT homozygotes can eclose and survive for up to 3 weeks, thereby allowing us to test the behavior of both homozygous and heterozygous mutants. In contrast to treatment with reserpine, which decreases motor activity (Pendleton et al 2000;Chang et al 2006), dVMAT mutant homozygotes show an increase in open-field locomotion. This difference further suggests that development in the absence of amines may result in adaptive changes in the fly's nervous system.…”

“…Remarkably, we find that homozygous mutants with little or no neuronal amine release not only survive, but show near normal or elevated responses to some environmental stimuli. This phenotype is in striking contrast to the enervating, and in some cases lethal effects of acute DVMAT inhibition with reserpine (Pendleton et al 1996(Pendleton et al , 2000Chang et al 2006), suggesting that the survival and behavior of the dVMAT mutants is the result of multiple adaptive changes in the nervous system.…”