GABA and GABA Receptors in Insects: Lessons from Periplaneta americana and Drosophila melanogaster

GABA (γ-aminobutyric acid) is the most abundant inhibitory neurotransmitter in the central nervous system of insects. GABAergic signal transduction is involved in the control and modulation of various vital functions such as salivation, locomotion, vision and olfaction, circadian timekeeping and sleep, arousal as well as learning and memory. GABA exerts its effects by binding to specific receptors, which are divided into GABAA and GABAB receptors. GABAA receptors are ligand-gated Cl− channels and molecular targets for a variety of small-molecule insecticides (polychlorocycloalkanes such as dieldrin, phenylpyrazoles such as fipronil, isoxazolines, and meta-diamides) that are widely used in agriculture. GABAB receptors are seven-transmembrane G-protein-coupled receptors. GABAB receptors function as obligate heteromers consisting of the two subunits, GABAB-R1 and GABAB-R2, whereby GABAB-R1 binds the ligand and GABAB-R2 is coupled to the G protein. Usually, adenylyl cyclase activity is inhibited via the Gαi subunits of heterotrimeric G proteins; this leads to a reduction in the intracellular cAMP level. This review summarizes the current knowledge on the molecular and pharmacological properties of insect GABA receptors. Finally, two established model organisms for studying the effects of GABA in insects are presented as examples. The American cockroach (Periplaneta americana) has a long tradition as an object to study GABAergic circuits in the olfactory pathway and the role of GABA in the control of salivary secretion. The fruit fly (Drosophila melanogaster) has proven to be an unsurpassed model system to study the effects of GABA and specific GABA receptors on a variety of physiological functions and behavioral processes. In particular, D. melanogaster is used as a disease model for several human diseases in which GABAergic signaling is involved.