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Lmo Mutants Reveal a Novel Role for Circadian Pacemaker Neurons in Cocaine-Induced Behaviors

Figure 1

Lmo Loss-of-Function Mutants Show Increased Sensitivity to Cocaine

(A) Cocaine phenotypes of various Lmo mutants. Male flies hemizygous for the indicated Lmo alleles (and their appropriate genetic controls) were exposed to 150 μg of cocaine and tested in the crackometer as described in Materials and Methods. Compared to their control (Ctl-1), EP1383 (p < 0.02) and EP1306 (p < 0.001) flies show significantly increased sensitivity to cocaine. Similarly, compared to their respective controls, pdrm and hdp flies are significantly more sensitive to cocaine (p < 0.001). Asterisks denote significant differences from controls (Student's paired t-test assuming equal variance); n = 20 experiments.

(B) Cocaine dose–response. EP1306 flies (filled squares) and pdrm flies (filled circles) and their respective controls were exposed to the indicated doses of cocaine. At each dose, the responses of EP1306 and pdrm flies are significantly higher than their controls (p < 0.001, n = 16–20 experiments).

(C) EP1306 flies show alterations in cocaine-induced locomotor patterns of activity. Flies were exposed to 0, 75, or 100 μg of cocaine, as indicated, for 1 min. Representative traces shown correspond to 30 s of recorded activity of about ten flies starting 1 min after the end of cocaine exposure (n ≥ 4). Top panels show response of control flies to indicated amounts of cocaine; bottom panels show activity of EP1306 flies after cocaine administration. Ctl-1 is EP1631, Ctl-2 is P[GAL4] line 8.142, and Ctl-3 is w1118.

Figure 1

doi: https://doi.org/10.1371/journal.pbio.0020408.g001