Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Hou, J. et al.

Repetitive exposures to nicotine induce a hyper-responsiveness via the cAMP/ PKA/CREB signal pathway in Drosophila.

Nicotine, in addition to acute effects, has long-lasting effects on mammalian behaviors, such as those leading to addiction. Here we present genetic and pharmacological evidence in Drosophila suggesting that repetitive exposures to nicotine induce a hyper-responsiveness through synthesis of new protein(s) via CREB-mediated gene transcription. Single exposure to volatilized nicotine dose-dependently inhibited the startle-induced climbing response. Compared with this effect of nicotine in wild-type flies, it was stronger in dunce, which has defective phosphodiesterase, and in wild-type flies treated with a phosphodiesterase inhibitor, whereas it was weaker in DC0, which has defective protein kinase A ( PKA), and in wild-type flies treated with a PKA blocker. Thus, the effect of nicotine is enhanced by a mechanism involving the cAMP/ PKA cascade. However, in wild-type flies, an increase in head cAMP was not detected within 2 min after single exposure to nicotine, during which the nicotine effect on the behavior was maximal. In wild-type flies, after repetitive exposures to nicotine, the nicotine effect was significantly enhanced and the head cAMP was elevated. The responsiveness to nicotine at second exposure increased with a 4 h interval but not with a 2 h interval, suggesting that the observed hyper-responsiveness was not due to accumulation of residual nicotine. Both enhancement of the nicotine effect and elevation of cAMP during repetitive exposures to nicotine were blocked by a protein synthesis inhibitor. Induction of a dominant negative CREB transgene also blocked the enhancement, suggesting that CREB-mediated gene transcription is required for the hyper-responsiveness.[1]

References

Repetitive exposures to nicotine induce a hyper-responsiveness via the cAMP/PKA/CREB signal pathway in Drosophila. Hou, J., Kuromi, H., Fukasawa, Y., Ueno, K., Sakai, T., Kidokoro, Y. J. Neurobiol. (2004) [Pubmed]

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