Rg. Pendleton et al., Effects of adrenergic agents on locomotor behavior and reproductive development in Drosophila, DRUG DEV R, 50(2), 2000, pp. 142-146
Inhibition of tyrosine hydroxylase, the rate-limiting enzyme in catecholami
ne biosynthesis, by alpha-methyl-p-tyrosine (alpha MT) at media concentrati
ons of 0.3-3.0 mM, markedly inhibited (>90%) fly reproduction and developme
nt as evidenced by progeny count. Under these conditions adult spontaneous
locomotor activity (SMA) was also dose-dependently reduced. However, no sig
nificant effects on behavior were observed at 0.3 mM. The behavioral effect
s of alpha MT 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-D
OPA. Treatment at 1 mM with the mammalian catecholamine receptor blockers p
ropranolol (beta(1)beta(2)), raclopride (D-2), SK&F 83566 (D-1), prazosin (
alpha(1)), and rauwolscine (alpha(2)) did not affect behavior. The two alph
a adrenoceptor inhibitors, however, markedly decreased fly development. The
se results suggest that the receptor mechanisms mediating the effects of ca
techolamines on behavior and development are different. The locomotor behav
ior of adult progeny of parents treated with the lowest doses of alpha MT a
nd reserpine described above was markedly suppressed by these drug treatmen
ts. This result indicates an increased sensitivity of the progeny to compou
nds which share the ability to deplete tissue catecholamines. Thus, alterat
ions in catecholamine function during development may have behavioral conse
quences in surviving organisms. (C) 2000 Wiley-Liss, Inc.