GABA-B receptors in Drosophila.

Drosophila melanogaster, the "fruit fly," is being increasingly used as an experimental model in neurosciences, including neuropharmacology. The advantages of Drosophila over typical mammalian models in neuropharmacology include better access to genetic manipulation and the availability of almost unlimited numbers of experimental subjects at relatively low cost and with minimal regulatory restrictions. Nevertheless, one should remain cognizant of the substantial differences between insects and mammals. Insects, including Drosophila, utilize gamma-aminobutyric acid (GABA) as a neurotransmitter and express both ionotropic GABA receptors and metabotropic GABA-B receptors. Before cloning of the Drosophila GABA-B receptors (subunits 1-3), it had been assumed that flies did not express these receptors since baclofen, a typical agonist for mammalian GABA-B receptors, does not produce any effects in insects. Subsequently, it was confirmed that cloned Drosophila GABA-B receptors exhibit a unique pharmacology. Using Drosophila as a model, it has been shown that GABA-B receptors are involved in the behavioral actions of alcohol and gamma-hydroxybutyric acid, and possibly in pain. Furthermore, recent research suggests that in flies these receptors may play an important developmental role and that they participate in olfaction and in regulation of circadian rhythms. Copyright 2010 Elsevier Inc. All rights reserved.