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. 2021 Mar 10;11:5549. doi: 10.1038/s41598-021-85002-1

Figure 5.

Figure 5

Effect of GPR139 agonist on fear memory recall and avoidance. (A) During pre-conditioning, fish were given a choice for their preferred colour, either yellow (Y) or white (W) coloured compartment. In total, a significantly higher number of fish preferred yellow coloured compartment during the pre-conditioning (P = 0.006). After conditioning to alarm substance (AS)-induced fear-like responses, the fish were administered with GPR139 agonist (JNJ-63533054, either 0.1 or 1 µg/g body weight, BW), and the following day (Day-3), their preference was assessed based on their total time spent in either AS-paired (originally preferred) or water-paired (originally non-preferred) compartment. (B) During the post-conditioning, the time spent in AS-paired compartment (blue dots) was significantly reduced in both controls (P = 0.0147 and P = 0.0185) and fish treated with 0.1 µg/g BW of GPR139 agonist (P = 0.0005) as compared to pre-conditioning period (red dots), indicating successful development of conditioned place avoidance. On the other hand, in fish treated with the higher dose (1 µg/g BW) of GPR139 agonist, there was no difference in the time spent in the preferred compartment between pre-conditioning and post-conditioning phase (P = 0.0519). (C) There was no dose-dependency in place avoidance (P = 0.8403). (D) During the post-conditioning period, the total time frozen in the AS-paired compartment was significantly reduced in all groups [controls (0.2% DMSO, P = 0.0143; 2% DMSO, P = 0.0197), 0.1 µg/g BW GPR139 agonist (P = 0.0013), 1 µg/g BW GPR139 agonist (P = 0.0459)]. (E) On the other hand, the time spent in the water-paired unpunished compartment (originally non-preferred compartment) was increased during the post-conditioned phase in control (0.2% DMSO, P = 0.0483, Cohen’s d = 0.9472) and the fish treated with 0.1 µg/g BW GPR139 agonist (P = 0.0118, Cohen’s d = 0.9155). However, in control (2% DMSO) and the fish treated with 1 µg/g BW GPR139 agonist, there was no significant change in the time spent in the water-paired unpunished compartment after the fear conditioning (control, P = 0.3086, Cohen’s d = 0.4686; 1 µg/g BW GPR139 agonist, P = 0.1072, Cohen’s d = 0.5877). *, P < 0.05; **, P < 0.01; n.s., no significant difference.