Fig. 1

Figure 1. Experimental design schematics. (A) Embryos at 48 hpf were treated to obtain the MTC of the drugs. (B) Exposure timeline of the drugs. (C) Synaptic localization of all genes examined. (D) Aggression testing using a test tank with a mirror. ADAMTS2: a disintegrin and metalloproteinase with thrombospondin motifs 2, AKT1: v-akt murine thymoma viral oncogene homolog 1, AMPA: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, CREB: cAMP responsive element binding protein, DA: dopamine, dpf: days post fertilization, hpf: hours post fertilization, MTC: maximum tolerated concentration, NMDA: N-methyl-D-aspartate, PI3K: phosphoinositide 3-kinase, SLC6A4: solute carrier family 6 member 4, 5-HT: 5-hydroxytryptamine.

Fig. 2

Figure 2. Altered gene expression in zebrafish larvae following exposure to MK801, DMP and morphine, and morphine withdrawal. (A) Effect of short-term (3-day) drug exposure on expression of akt1 (F (3,32) = 1.386, p = 0.265), pi3k (F (3,32) = 1.127, p = 0.299), slc64a (F (3,32) = 1.721, p = 0.182), creb1 (F (3,32) = 0.522, p = 0.667) and adamst2 (F (3,32) = 2.771, p = 0.058). (B) Effect of long-term (10-day) drug exposure on expression of akt1 (F (3,32) = 14.546, p < 0.001), pi3k (F (3,32) = 6.650, p < 0.001), slc64a (F (3,32) = 25.115, p < 0.001), creb1 (F (3,32) = 29.607, p < 0.001) and adamst2 (F (3,32) = 90.337, p < 0.001). (C) Effect of short-term morphine exposure followed by 5-day withdrawal on expression of akt1 (t (16) = 8.945, p = 0.003), pi3k (t (16) = 8.082, p = 0.001), slc6a4 (t (16) = 5.591, p = 0.001), creb1 (t (16) = 6.394, p = 0.001), adamts2 (t (16) = 0.306, p = 0.064). (D) Effect of long-term morphine exposure followed by 5-day withdrawal on expression of akt1 (t (16) = 8.945, p = 0.003), pi3k (t (16) = 27.493, p < 0.001), slc6a4 (t (16) = 2.445, p = 0.058), creb1 (t (16) = 6.102, p < 0.001), adamts2 (t (16) = 5.709, p = 0.001). Data expressed as mean ± SEM, n = 50 of 3 independent experiments. Different lowercase letters indicate statistically significant values, p < 0.05. DMP: domperidone.
Fig. 3

Figure 3. Effects of (A) short-term (F (3,32) = 22.035, p < 0.001) and (B) long-term (F (3,32) = 108.164, p < 0.001) exposure to MK801, DMP and morphine, and (C) short-term (t (16) = 12.465, p = 0.003) (D) and long-term (t (16) = 9.964, p = 0.029) morphine withdrawal on whole-body cAMP concentration (ng/mL) in zebrafish larvae. Data expressed as mean ± SEM, n = 50 of 3 independent experiments. Different lowercase letters indicate statistically significant values, p < 0.05. cAMP: cyclic adenosine monophosphate, DMP: domperidone.
Fig. 4

Figure 4. Effects of (A) short-term (F (3,32) = 22.035, p < 0.001) and (B) long-term (F (3,32) = 108.164, p < 0.001) exposure to MK801, DMP and morphine, and (C) short-term (t (16) = 12.465, p = 0.003) (D) and long-term (t (16) = 9.964, p = 0.029) morphine withdrawal on whole-body cAMP concentration (ng/mL) in zebrafish larvae. Data expressed as mean ± SEM, n = 50 of 3 independent experiments. Different lowercase letters indicate statistically significant values, p < 0.05. DMP: domperidone.
Fig. 5

Figure 5. Effects of (A) short-term (F (3,32) = 16.064, p < 0.001) and (B) long-term (F (3,32) = 11.777, p < 0.001) exposure to MK801, DMP and morphine, and (C) short-term (t (16) = 4.531, p = 0.001) and (D) long-term (t (16) = 2.032, p = 0.019) morphine withdrawal on whole-body serotonin concentration in zebrafish larvae. Data expressed as mean ± SEM, n = 50 of 3 independent experiments. Different lowercase letters indicate statistically significant values, p < 0.05. DMP: domperidone.
Fig. 6

Figure 6. Mirror biting frequency of zebrafish larvae following (A) short-term (F (3,140) = 19.490, p = 0.001) and (B) long-term (F (3,140) = 56.224, p = 0.001) exposure to MK801, DMP and morphine, and (C) short-term morphine exposure followed by 5-day withdrawal (t (70) = 5.278, p = 0.001) and (D) long-term morphine exposure followed by 5-day withdrawal (t (70) = 8.830, p = 0.005). Data expressed as mean ± SEM, n = 36 of 3 independent experiments. Different lowercase letters indicate statistically significant values, p < 0.05. DMP: domperidone.
Acknowledgments
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