Naloxone-precipitated morphine withdrawal results in a characteristic morbidity, including anxiety, nausea, insomnia, hot and cold flashes, muscle aches, perspiration, diarrhea, etc. As shown in Figure 5, most of the observed behavioral signs, the backward walking, chewing, diarrhea, jump, ptosis, tremor, wet dog shake and weight loss were significantly alleviated in EphB1-/- mice compared to those in WT mice except that the paw tremor in EphB1-/- mice was not different from that in WT mice (Fig. 5I). Here, EPHB1 is linked to insomnia.