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On the pharmacological phenocopying of memory mutations inDrosophila: Alkylxanthines accelerate memory decay

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Abstract

Theophylline and 3-isobutyl-1-methylxanthine, two cyclic nucleotide phosphodiesterase inhibitors, when fed to wild-typeDrosophila adults, cause the rapid decay of learning index after training in a shock-odor learning paradigm. The drugs practically do not affect the olfactory acuity of flies, hence they influence the learning/memory process itself. The time courses of memory decay resemble those of the memory mutantsrutabaga andamnesiac and, to a lesser extent,dunce 2 anddunce M11. Theophylline further deteriorates the learning performance ofdunce M11. Biochemical characterization of the inhibition of the two major phosphodiesterase isoenzymes inDrosophila by theophylline predicts only a slight inhibition of these enzymesin vivo, in accordance with the unchanged level of cAMP in wild-type fly heads during drug feeding. 8-Phenyltheophylline, an adenosine receptor antagonist in mammals, slightly retards memory decay in the wild-type. It is suggested that alkylxanthines induce memory decay inDrosophila by interfering with cAMP dynamics at more than one point of its metabolism.

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This work was supported by Grants OTKA and OKKFT Tt to P.F.

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Asztalos, Z., Lossos, M. & Friedrich, P. On the pharmacological phenocopying of memory mutations inDrosophila: Alkylxanthines accelerate memory decay. Behav Genet 21, 495–511 (1991). https://doi.org/10.1007/BF01066727

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Key Words

  • Drosophila
  • memory mutants
  • cyclic AMP
  • phosphodiesterase
  • olfaction