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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.
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Pendleton et al. (2000) studied this question.
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