The CCK1 receptor antagonist blocked the inhibitory effects of exogenous CCK-8 on naloxone precipitated cAMP overshoot after chronic morphine exposure. The SH-SY5Y cells were co-pretreated with L-364,718(1 and 10 μM) or LY-288,513(1 and 10 μM) and CCK-8 (1 μM) plus morphine (10 μM) for 48 h. After the removal of the drugs, naloxone (10 μM, 15 min) was added for the induction of the cAMP overshoot. The control group was the no CCK-8 and CCK receptor antagonist treated cells (Sal + Sal). The results of the cAMP level are represented as the percentage of cAMP content relative to the control group. The data are the mean ± S.D. of three separate experiments, performed in duplicate. ##P < 0.01, compared with the Sal + Sal group by t-test; **P < 0.01, ***P < 0.001 as compared with the Sal + CCK-8 group by one-way ANOVA followed by Dunnett’s t-test.