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neurotransmitter acting in alcohol abuse; glutamate, serotonin, and GABA also
may be involved. Furthermore, four of the five circadian genes ( period + , clock + ,
cycle + , and doubletime + ) in D. melanogaster influence the fly's responsiveness to
cocaine and suggest a biochemical regulator of cocaine sensitization ( Andretic
et al. 1999 ).
Resistance to ethanol in D. melanogaster appears to be determined by mul-
tiple genetic components. Singh and Heberlein (2000) analyzed 23 mutant fly
strains with different responses to ethanol and the effects of acute ethanol
exposure on Drosophila locomotor behaviors are “remarkably similar to those
described for mammals.” Thus, study of Drosophila “may pave the way for an
in-depth study of the genes involved in acute and chronic effects of ethanol”
( Bellen 1998 ). Bainton et  al. (2000) showed that, as in mammals, dopaminergic
pathways in Drosophila play a role in modulating specific behavioral responses
to cocaine, nicotine, or ethanol.
Drosophila flies can sleep, and they have become a model for understanding
sleep in insects and other animals ( Hendricks et al. 2000; Greenspan et al. 2001;
Harbison et al. 2009a,b; Donlea et al. 2011, 2012; Soshnev et al. 2011 ). Flies that
are “resting” choose a preferred location, become immobile for periods of up
to 157 minutes at a particular time in the circadian day, and are relatively unre-
sponsive to sensory stimuli. When rest is prevented, the flies tend to rest despite
stimulation and exhibit a “rest rebound.” In fact, flies subjected to long-term
sleep deprivation may die. Drugs that affect sleep in mammals alter “rest” in
flies, suggesting conserved neural mechanisms.
“During sleep, an animal cannot forage for food, take care of its young,
procreate or avoid the dangers of predation, indicating sleep must serve
an important function” ( Greenspan et  al. 2001 ), although there is no agree-
ment yet as to its function(s) ( Harbison et  al. 2009b ). Hypotheses proposed to
explain the evolutionary maintenance of sleep include conservation of energy
by reduced expenditure of nutrients, restoration of brain glycogen, and mainte-
nance of homeostasis of synapses ( Harbison et al. 2009b ). Sleep is important in
learning and memory ( Donlea et  al. 2011 ). Sleep disorders in humans are com-
mon, but the genes underlying these disorders are difficult to study ( Kolker and
Turek 1999 ). Analysis of Drosophila behavior at the molecular level offers prom-
ise of elucidating this evolutionarily important aspect of survival, and muta-
genesis studies suggest that many genes (perhaps as many as 1000) affect sleep
( Harbison et  al. 2009a,b ). Harbison et  al. (2009a) analyzed variation in sleep in
40 highly inbred lines of D. melanogaster and found many variable genes with
only a few having large effects. The data suggest that, like mammals, regulation
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