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. 2020 Oct 14;11:577155. doi: 10.3389/fpsyt.2020.577155

Figure 3.

Figure 3

Continuous high frequency-DBS (HF-DBS) of anterior insula (AI) accelerates extinction and prevents priming-induced relapse of morphine-induced conditioned place preference (CPP). (A) Experimental scheme. After an 8-day morphine-CPP training, the rats were bilaterally implanted with DBS electrodes to AI (morphine-DBS and morphine-DBS-sham groups) followed by a 5-day recovery. All groups of rats were further subjected to drug-free daily extinction sessions (Day 16–25). HF-DBS (130 Hz, 150 μA, 90 μs) was continuously applied in morphine-DBS rats. Twenty-four hours after the complete extinction, all groups of rats received a priming dose of morphine (2 mg/kg) followed by a CPP test. (B) The morphine-DBS group expressed the complete extinction of morphine-induced CPP on day 20, which were 5 days earlier than both morphine and morphine-DBS-sham groups (Two-way repeated-measures ANOVA, phase: F(12, 29) = 195.486, p < 0.001; treatment: F(3, 40) = 152.651, p < 0.001; interaction: F(36, 93) = 5.392, p < 0.001; Post hoc test, Extinction day 5: p < 0.001 for morphine-DBS vs. morphine-DBS-sham and morphine). On day 26, the priming injection of morphine failed to reinstate morphine-induced CPP in the morphine-DBS group (p < 0.001 for morphine or morphine-DBS-sham vs. saline or morphine-DBS). Data are shown as mean with SEM. Two-way repeated ANOVA with post hoc Bonferroni test. ≠p < 0.001, Saline vs. morphine or morphine-DBS or morphine-DBS-sham. ***p < 0.001, morphine-DBS vs. morphine or morphine-DBS-sham. #p < 0.001, morphine or morphine-DBS-sham vs. saline or morphine-DBS. n = 12 for saline and morphine, n = 9 for morphine- DBS -sham and n = 11 for morphine-DBS groups.