GABAergic modulation of motor-driven behaviors in juvenile Drosophila and evidence for a nonbehavioral role for GABA transport.
We have identified specific GABAergic-modulated behaviors in the juvenile stage of the fruit fly, Drosophila melanogaster via systemic treatment of second instar larvae with the potent GABA transport inhibitor DL-2,4-diaminobutyric acid (DABA). DABA significantly inhibited motor-controlled body wall and mouth hook contractions and impaired rollover activity and contractile responses to touch stimulation. The perturbations in locomotion and rollover activity were reminiscent of corresponding DABA-induced deficits in locomotion and the righting reflex observed in adult flies. The effects were specific to these motor-controlled behaviors, because DABA-treated larvae responded normally in olfaction and phototaxis assays. Recovery of these behaviors was achieved by cotreatment with the vertebrate GABA(A) receptor antagonist picrotoxin. Pharmacological studies performed in vitro with plasma membrane vesicles isolated from second instar larval tissues verified the presence of high-affinity, saturable GABA uptake mechanisms. GABA uptake was also detected in plasma membrane vesicles isolated from behaviorally quiescent stages. Competitive inhibition studies of [3H]-GABA uptake into plasma membrane vesicles from larval and pupal tissues with either unlabeled GABA or the transport inhibitors DABA, nipecotic acid, or valproic acid, revealed differences in affinities. GABAergic-modulation of motor behaviors is thus conserved between the larval and adult stages of Drosophila, as well as in mammals and other vertebrate species. The pharmacological studies reveal shared conservation of GABA transport mechanisms between Drosophila and mammals, and implicate the involvement of GABA and GABA transporters in regulating physiological processes distinct from neurotransmission during behaviorally quiescent stages of development.
Leal
Sandra M
SM
Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 S. Grand Blvd., St. Louis, Missouri 63103, USA.
Kumar
Nitin
N
Neckameyer
Wendi S
WS
D000367:Age Factors; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster; D050485:GABA Plasma Membrane Transport Proteins; D058785:GABA-A Receptor Agonists; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology; D014110:Touch / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000502:physiology*
D000613:Aminobutyrates; D050485:GABA Plasma Membrane Transport Proteins; D058785:GABA-A Receptor Agonists; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D011963:Receptors, GABA-A; C005959:2,4-diaminobutyric acid; D005680:gamma-Aminobutyric Acid