Zebrafish: A Predictive Model for Assessing Seizure Liability - Zebrafish: Methods for Assessing Drug Safety and Toxicity - page 167

350

300

250

200

150

100

50

0

0 100 200 300 400
4-AP concentration (μM)

Figure 13.3 Peak D was concentration dependent for 4-AP. Using three 4-AP concentrations, peak D
was concentration dependent. Each point represents meanSE ( N ¼20).

lidocaine, a sedative, did not induce movement, D was“0”andnopeak D was
observed.
Based on these results, for 4-AP, strychnine hemisulfate, methoxychlor,
and amoxapine, increase in peak D was concentration dependent (Fig. 13.3, example,
4-AP). For PTZ, picrotoxin, aminophylline hydrate, and bicucullinemethiodide, peak
D plateaued at the second highest compound concentration.
Based on results shown in Table 13.2, we then compared peak D for
compound-treated animals with D for control animals at the same time point,
as described in Section 13.2. Percent increase in D compared to controls was
1776% (PTZ), 3707% (4-AP), 1777% (picrotoxin), 1531% (strychnine hemi-
sulfate), 1521% (methoxychlor), 650% (amoxapine), 461% (aminophylline hy-
drate), 92% (bicuculline methiodide), 174% (enoxacin), and 82% (lidocaine).

Statistical analysis using Student's t -test showed that PTZ, 4-AP, picrotoxin,
strychnine hemisulfate, methoxychlor, amoxapine, aminophylline hydrate, and
bicuculline methiodide induced significant effects ( P

< 0.05), whereas effect of

enoxacin was insignificant ( P 0.05). Lidocaine, the negative control compound,

did not induce movement and D was “0”. Therefore, compared to movement of
carrier control animals at the same time point, percent increase was negative, as
shown in Fig. 13.4.
Based on percent increase in peak D , we ranked compound effects on zebrafish
high-speed movement as 4-AP

>

> picrotoxin ¼ PTZ ¼ strychnine hemisulfate ¼

methoxychlor bicuculline methiodide.

Taking into consideration the error bars in Fig. 13.4, effects on high-speed movement
for PTZ, picrotoxin, strychnine, and methoxychlor were considered the same, and
effects of amoxapine and aminophylline hydrate on high-speed movement were
considered the same. The effect of enoxacin was insignificant.

> amoxapine ¼ aminophylline hydrate >