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Abstract

The brain of the adult fruit fly, Drosophila melanogaster, contains tyrosine hydroxylase, the rate-limiting enzyme required for catecholamine biosynthesis, as well as dopa decarboxylase. Catecholamines, principally dopamine, are also present. We have previously shown that pharmacological inhibition of tyrosine hydroxylase with alpha-methyl-p-tyrosine results in a dose-related inhibition of locomotor activity in adult organisms. Similar results were found with reserpine, a well-known inhibitor of catecholamine uptake into storage granules. The drug-induced inhibition could be prevented in each case by the concomitant administration of L-dopa. The single-copy gene coding for tyrosine hydroxylase in Drosophila is pale (ple). Both null and temperature-sensitive loss of function mutant alleles of ple are recessive embryonic lethals. Heterozygous null mutant flies have normal locomotor activity demonstrating that only a single dose of the wild type form of ple is required to support normal function. Both hemizygous and homozygous temperature-sensitive ple mutants (ple(ts1)) also show normal locomotor activity at the permissive temperature for this mutant allele (18 degrees C), which progressively declines as the temperature is increased to its restrictive level (29 degrees C). These abnormal locomotor effects are reversible by L-dopa. Thus the effects on locomotor activity resulting from the pharmacological inhibition of catecholamine synthesis or storage are the same as those resulting from lack of tyrosine hydroxylase expression. These findings indicate that brain catecholamine loss decreases locomotor activity in the fly, as it does in mammals, and demonstrate the ability of functional genomic studies to mimic that of pharmacological inhibition of enzyme function or other similar processes.

PIP2 regulates psychostimulant behaviors through its interaction with a membrane protein

“…Locomotion is an elemental behavior regulated by DA across species, including Drosophila melanogaster 8,9,33,34 . Recently, locomotion in flies has been adopted to evaluate molecular discoveries of AMPH actions mechanistically in vivo 8,9 .…”

Queen pheromone modulates brain dopamine function in worker honey bees

“…But what impact, if any, do these changes have on the behavior of young worker bees? Because a large body of evidence implicates dopamine in the regulation of locomotor activity in insects (13,14,(16)(17)(18), we examined QMP's effects on activity levels in the bee. Individual bees were placed in a Petri dish with a grid pattern on the floor of the dish.…”

“…HVA (4-hydroxy-3-methoxyphenylethanol) bears a striking structural resemblance to dopamine (see Fig. 1 Right), a biogenic amine that plays a central role in insect behavioral regulation and motor control (11)(12)(13)(14)(15)(16)(17)(18). The presence of this compound within the pheromone blend suggested to us that dopamine function in the brain of recipient bees might be affected by exposure to QMP.…”

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].…”