Summary
We have studied the effect of formamidines onDrosophila melanogaster. Low concentrations of formamidines are toxic to adultDrosophila. A mutant with reduced cAMP synthesis displays increased resistance to the toxin. Formamidines also reduce viability ofDrosophila eggs and retard imago eclosion. At sublethal concentrations, formamidines markedly affect the flies' behavior. Upon injection, the compounds increase muscle activity. Upon feeding, formamidines induce motor excitation, reduce phototaxis and impair olfactory learning without affecting the ability to recognize an olfactory cue. In vitro, two formamidines were found to inhibit octopamine-stimulated adenylate cyclase without affecting the basal activity of the enzyme, while a third one was found to stimulate adenylate cyclase; this stimulation was blocked by phentolamine and to a lesser degree by propranolol, thus resembling the effect of octopamine. The binding of [3H]octopamine toDrosophila head membranes was also inhibited. Taken together, our results indicate that formamidines interact with octopaminergic systems inDrosophila, exert both peripheral and central effects in the fly, and could be used to dissect the roles of octopamine in development and behavior, including behavioral plasticity. The results also suggest that formamidines could be used to select mutants in aminergic transmission and in the cAMP cascade.
Similar content being viewed by others
Abbreviations
- CDMF :
-
chlordimeform
- DMPF :
-
N,N-dimethyl-N2-(2,4-dimethylphenyl) formamidine
References
Aceves-Pina EO, Booker R, Duerr JS, Livingstone MS, Quinn WG, Smith RF, Sziber PP, Tempel BL, Tully TP (1983) Learning and memory inDrosophila, studied with mutants. Cold Spring Harbor Symp Quant Biol 48:831–840
Beeman RW (1982) Recent advances in mode of action of insecticides. Annu Rev Entomol 27:253–281
Benzer S (1967) Behavioral mutants ofDrosophila isolated by countercurrent distribution. Proc Natl Acad Sci USA 58:1112–1119
David JC, Coulon JF (1985) Octopamine in invertebrates and vertebrates. A review. Prog Neurobiol 24:141–185
Downer RGH, Gole JWD, Orr GL (1985) Interaction of formamidines with octopamine-, dopamine- and 5-hydroxytryptamine-sensitive adenylate cyclase in nerve cord ofPeriplaneta americana. Pest Sci 16:472–478
Dudai Y (1977) Properties of learning and memory inDrosophila melanogaster. J Comp Physiol 114:69–89
Dudai Y (1982) High-affinity octopamine receptors revealed inDrosophila by binding of [3H]octopamine. J Neurochem 38:1551–1558
Dudai Y (1986) cAMP and learning inDrosophila. Adv Cyc Nucl Prot Phosph Res 20:343–361
Dudai Y, Zvi S (1985) Multiple defects in the adenylate cyclase ofrutabaga, a memory mutant ofDrosophila. J Neurochem 45:355–364
Dudai Y, Nahum-Zvi S, Haim-Granot N (1980) Cholinergic pharmocology ofDrosophila melanogaster: Comparison of in vivo to in vitro studies. Comp Biochem Physiol 65C: 135–138
Dudai Y, Uzzan A, Zvi S (1983) Abnormal activity of adenylate cyclase in theDrosophila memory mutantrutabaga. Neurosci Lett 42:207–212
Dudai Y, Zvi S, Segel S (1984) A defective conditioned behavior and a defective adenylate cyclase in theDrosophila mutantrutabaga. J Comp Physiol A 155:569–576
Dudai Y, Buxbaum Y, Corfas G, Orgad S, Segal D, Sher B, Uzzann A, Zvi S (1986) Defective cAMP metabolism and defective memory inDrosophila. Acta Biochim Biophys Hung 21:177–192
Elgin SCR, Miller DW (1978) Mass rearing of flies and mass production and harvesting of embryos. In: Ashbruner M, Wright TRF (eds) The genetics and biology ofDrosophila, vol 2a. Academic Press, London, pp 112–121
Evans PD, Gee JD (1980) Action of formamidine pesticides on octopamine receptors. Nature 287:60–62
Folkers E, Spatz HCh (1984) Visual learning performance ofDrosophila is altered by neuropharmaca affecting phosphodiesterase activity and acetylcholine transmission. J Insect Physiol 30:957–965
Gole JWD, Orr GL, Downer RGH (1983) Interaction of formamidines with octopamine sensitive adenylate cyclase receptor in the nerve cord ofPeriplaneta americana. Life Sci 32:2939–2947
Hall JC (1982) Genetics of the nervous system inDrosophila. Q Rev Biophys 15:223–479
Hollingworth RM (1976) Chemistry, biological activity, and uses of formamidine pesticides. Environ Health Perspect 14:57–69
Hollingworth RM, Murdock LL (1980) Formamidine pesticides: octopamine-like actions in a firefly. Science 208:74–76
Kandel ER, Schwartz JH (1982) Molecular biology of learning: Modulation of transmitter release. Science 218:433–443
Kety SS (1970) The biogenic amines in the central nervous system: Their possible roles in arousal, emotion and learning. In: Schmitt FO (ed) The neurosciences, 2nd study program Rockefeller University Press, New York pp 324–336
Lewis EB (1960) A new standard food medium. Drosophila Inf Ser 34:117–118
Leysen JE, Gommeren W (1981) Optimal conditions for [3H]apomorphine binding and anomalous equilibrium binding of [3H]apomorphine and [3H]spiperone to rat striatal membranes: Involvement of surface phenomena versus multiple binding sites. J Neurochem 36:201–219
Livingstone MS, Sziber PP, Quinn WG (1984) Loss of calcium/calmodulin responsiveness in adenylate cyclase ofrutabaga, aDrosophila learning mutant. Cell 37:205–215
Mercer AR, Menzel R (1982) The effect of biogenic amines on conditioned and unconditioned responses to olfactory stimuli in the honeybee,Apis mellifera. J Comp Physiol 145:363–368
Nathanson JA (1985) Characterization of octopamine sensitive adenylate cyclase: Elucidation of a class of potent and selective octopamine-2 receptor agonists with toxic effects in insects. Proc Natl Acad Sci USA 82:599–603
Nathanson JA, Hunnicutt EJ (1981) N-demethylchlordimeform. A potent partial agonist of octopamine-sensitive adenylate cyclase. Mol Pharmacol 20:68–75
Quinn WG, Harris WA, Benzer S (1974) Conditioned behavior inDrosophila melanogaster. Proc Natl Acad Sci USA 71:708–712
Salomon Y (1979) Adenylate cyclase assay. Adv Cyclic Nucleoticle Res 10:35–55
Tully T, Quinn WG (1985) Classical conditioning and retention in normal and mutantDrosophila melanogaster. J Comp Physiol A 157:263–277
Uzzan A, Dudai Y (1982) Aminergic receptors inDrosophila melanogaster: Responsiveness of adenylate cyclase to putative neurotransmitters. J Neurochem 38:1542–1550
Wu CF, Berneking JM, Barker DL (1983) Acetylcholine synthesis and accumulation in the CNS ofDrosophila larvae: Analysis of shibirets, a mutant with a temperature-sensitive block in synaptic transmission. J Neurochem 40:1386–1396
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dudai, Y., Buxbaum, J., Corfas, G. et al. Formamidines interact withDrosophila octopamine receptors, alter the flies' behavior and reduce their learning ability. J. Comp. Physiol. 161, 739–746 (1987). https://doi.org/10.1007/BF00605015
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00605015