St. Louis University School of Medicine, St. Louis MO 63104 USA,
In addition to its physiological requirement in normal development, dopamine acts as a signalling molecule in the nervous system. To elucidate the role of this transmitter in the modulation of different behaviors, we have altered dopamine levels via manipulation of tyrosine hydroxylase, the first and rate-limiting enzyme in dopamine biosynthesis.
Perturbation of dopamine levels by inhibition of
tyrosine hydroxylase activity was accomplished
in Drosophila melanogaster larval instars by
feeding an enzyme inhibitor for a 24 hour
period. Behavioral assays performed
immediately after treatment demonstrated that
larval phototaxis, salt aversion and heptanol
preferences were unaffected by reduced levels of
dopamine. Within a few hours off treatment,
however, 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.
Specific environmental stresses result in altered
dopamine levels which are a reflection of
changes in dopamine synthesis. As observed in
mammals, newly eclosed adult flies exposed to
cold (4oC) stress for up to 24 hours showed a
significant increase in dopamine levels and in
tyrosine hydroxylase expression. In contrast,
dopamine levels and tyrosine hydroxylase
expression decline with increasing age, with
significant differences between the sexes.
Using the approaches described above, we have
also determined that dopamine plays a
fundamental role in reproductive success.