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. 2018 Nov 14;50(11):148. doi: 10.1038/s12276-018-0175-1

Fig. 5. l-CDL antagonizes spinal D2DR to attenuate morphine tolerance in mice by inhibiting PI3K/Akt signaling in a MOR-dependent manner.

Fig. 5

a, b Intrathecal administration of the PI3K inhibitor LY 294002 (5 μg/10 μl) attenuated morphine tolerance, while LY 294002 (5 μg/10 μl) alone did not affect the pain threshold of naïve mice. The analgesia was further reported as area under the curve (AUC) units. Data are presented as means ± SE. n = 12, *P < 0.05, **P < 0.01, compared with the morphine group. c Intrathecal administration of LY 294002 (5 μg/10 μl) reduced the increase in p-Akt levels in the spinal cord. d, e Intrathecal administration of the D2DR siRNA and l-CDL reduce p-Akt levels in the spinal cord, while intrathecal administration of the D2DR conRNA had no effect. f Intrathecal administration of the MOR antagonist CTOP (1 ng/10 μl) reversed the increased p-Akt levels in the spinal cord. Data are presented as means ± SE. n = 4, #P < 0.05, ##P < 0.01, compared with the control group; *P < 0.05, **P < 0.01, compared with the morphine group. g, h Intrathecal administration of the PI3K inhibitor LY 294002 attenuated DAMGO-induced tolerance. All spinal cords were collected on day 7, 30 min after chronic morphine exposure. Data are presented as means ± SE. n = 12, *P < 0.05, **P < 0.01, compared with the DAMGO group