Figure 6.
Antipsychotics selectively rescue the defective habituation of btk mutants. Habituation indices quantifying the difference in footshock avoidance following exposure to the indicated number of stimuli from that of same genotype naive flies are shown as the mean ± SEM for the indicated number of repetitions (n). Asterisks indicate significant differences from controls as detailed in the text. A, Clozapine restores the defective habituation of btkM1 homozygotes. Compared with vehicle-treated mutants that do not habituate to 15 footshocks (0), habituation was significantly improved after treatment with 5 and 10 μm clozapine. n ≥ 9. B, Clozapine restores the defective habituation of btkM1/M2 hetero-allelics, which present a strong habituation defect if treated only with vehicle (0). Clozapine at 5 and 10 μm restored habituation to 15 footshocks. n ≥ 8 for all groups. C, Risperidone restores the defective habituation of btkM1 homozygotes. The strong habituation defect to 15 shocks of vehicle-treated mutant homozygotes was reversed after treatment with 0.1, 1, and 10 μm risperidone. n ≥ 9 for all groups. D, The habituation defect precipitated by adult-limited pan-MB abrogation of dBtk is barely reversible by 5 μm, but restored with 10 μm clozapine compared with vehicle-treated animals (0). n ≥ 8 for all groups. E, Clozapine (10 μm) and risperidone (10 μm) restore the defective habituation phenotype precipitated by adult-limited abrogation of dBtk in α′/β′ neurons. n≥9 for all groups. F, Clozapine (10 μm) and risperidone (10 μm) do not affect the performance of flies where adult-limited abrogation of dBtk in α/β neurons. n ≥ 9 for all groups. I, Clozapine (10 μm) in control flies does not induce premature habituation after 6 shocks, or a change in habituation after 15 such stimuli relative to vehicle (0)-treated controls. n ≥ 9 for all groups. J, Risperidone (10 μm) in control flies does not induce premature habituation after 6 shocks, but yields elevated habituation after 15 such stimuli relative to vehicle (0)-treated controls. n ≥ 9 for all groups. G, Clozapine selectively restores the defective, but not the premature habituation of btkM1 homozygotes. Clozapine did not change the premature habituation to 6 or 10 stimuli, but reversed the habituation failure after 15 footshocks. n ≥ 10 for all groups. H, Risperidone restores the defective habituation, but also enhances the premature habituation of btkM1 homozygotes. Risperidone rescued the habituation defect after 15 stimuli, but also resulted in significantly higher habituation scores after 6 and 10 footshocks. n ≥ 10 for all groups.