Speciation: New Migratory Direction Provides Route toward Divergence

overcome. This result is especially intriguing since it could mean that flies drink despite an aversive reaction to the ethanol-containing solution. To test this possibility more directly, Devineni and Heberlein [6] presented flies with quinine, an aversive tasting compound. Flies avoid drinking quinine-containing food (Figure 1B), and the authors found that, indeed, when quinine was added to ethanol-containing food, they initially avoided the cocktail. Over the next four days, though, they started preferring the ethanol/quinine food over regular food, while still avoiding quinine food versus regular food (Figure 1C). These findings indicate that over time flies are willing to ‘suffer’ adverse consequences, or at least taste, in order to drink ethanol. After showing that flies escalate their drinking, and are willing to overcome adversity for it, Devineni and Heberlein [6] set out to test whether flies would show relapse behavior. Relapse is defined as the reinstatement of drug-taking behavior after a period of (forced) abstinence in a previously addicted individual. To do this, flies were fed ethanol to establish a strong preference, and then they were fed sugar-containing food only for one, or three days. After this forced abstinence, when they were given a choice again between sucrose/yeast solution with or without ethanol, they immediately returned to strong ethanol-preference, and did not show the low preference typical for naı̈ve flies. Thus, flies show escalating drinking behavior, are willing to overcome adverse taste to drink, and show relapse-like behavior after forced abstinence. Repeated drug-taking results in tolerance — more drug needs to be consumed in order to attain the same subjective and physiological responses. Tolerance is one of the diagnostic criteria for addiction, and since it reflects a nervous system adaptation, is believed to play a role in the development of addiction. Flies develop tolerance to repeat ethanol administration [9,10], and a collection of Drosophila learning and memory mutants showed a high incidence of ethanol tolerance defects [11]. Of the 27 sensitivity and tolerance mutants Devineni and Heberlein [6] then tested for ethanol preference, one, krasavietz, showed a preference defect. It is surprising that only one of these mutants would have an ethanol preference defect, given that many mouse mutants with altered naı̈ve ethanol responses show changes in drinking behavior too [4]. Nevertheless, the data show that ethanol-drinking in flies is a genetically tractable behavior, and it will be interesting to see in the future whether pathways that are important in naı̈ve alcohol sensitivity and in the development of tolerance play a vital role in determining whether flies like to drink. The new study [6] will certainly help us on the way towards understanding the molecular and genetic underpinnings of why flies, and some of us humans, like to drink and may become addicted. References 1. American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders (Washington, DC: American Psychiatric Association). 2. Goldman, D., Oroszi, G., and Ducci, F. (2005). The genetics of addictions: uncovering the genes. Nat. Rev. Genet. 6, 521–532. 3. Schuckit, M.A. (1994). Low level of response to alcohol as a predictor of future alcoholism. Am. J. Psych. 151, 184–189. 4. Crabbe, J.C., Phillips, T.J., Harris, R.A., Arends, M.A., and Koob, G.F. (2006). Alcohol-related genes: contributions from studies with genetically engineered mice. Addic. Biol. 11, 195–269. 5. Cadieu, N., Cadieu, J.-C., El Ghadraoui, L., Grimal, A., and Lambœuf, Y. (1999). Conditioning to ethanol in the fruit fly — a study using an inhibitor of ADH. J. Insect Physiol. 45, 579–586. 6. Devineni, A.V., and Heberlein, U. (2009). Preferential ethanol consumption in Drosophila models features of addiction. Curr. Biol. 19, 2126–2132. 7. Cami, J., and Farre, M. (2003). Drug addiction. New Engl. J. Med. 349, 975–986. 8. Ja, W., Carvalho, G., Mak, E., De La Rosa, N., Fang, A., Liong, J., Brummel, T., and Benzer, S. (2007). Prandiology of Drosophila and the CAFE assay. Proc. Natl. Acad. Sci. USA 104, 8253–8256. 9. Scholz, H., Ramond, J., Singh, C.M., and Heberlein, U. (2000). Functional ethanol tolerance in Drosophila. Neuron 28, 261–271. 10. Atkinson, N.S. (2009). Tolerance in Drosophila. J. Neurogenet. 23, 293–302. 11. Berger, K., Kong, E.C., Dubnau, J., Tully, T., Moore, M.S., and Heberlein, U. (2008). Ethanol sensitivity and tolerance in long-term memory mutants of Drosophila melanogaster. Alcohol. Clin. Exp. Res. 32, 895–908.