On the pharmacological phenocopying of memory mutations inDrosophila: Alkylxanthines accelerate memory decay |
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Authors: | Zoltán Asztalos Marianna Lossos Peter Friedrich |
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Affiliation: | (1) Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, P.O. Box 7, H-1518 Budapest, Hungary |
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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,dunce2 anddunceM11. Theophylline further deteriorates the learning performance ofdunceM11. 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.This work was supported by Grants OTKA and OKKFT Tt to P.F. |
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Keywords: | Drosophila memory mutants cyclic AMP phosphodiesterase olfaction |
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