Figure 8. mGlu2 and mGlu3 NAM each reverse chronic stress-induced anhedonia.
(A) Mice received the stress hormone CORT in the drinking water for 4 weeks. Behavioral studies were conducted 1-2 weeks after the cessation of CORT treatment. The mGlu2 NAM VU6001966 (VU966; 10 mg/kg), mGlu3 NAM VU0650786 (VU786; 30 mg/kg), or vehicle was administered 24 hours prior to the sucrose preference test, and 45 minutes before the TST and FST. Behavioral assays were separated by 3 days and mice remained in the same treatment group for all tests. (B) Acute treatment with either VU6001966 or VU0650786 reversed CORT-induced anhedonia (ANOVA main effect of NAM: F2,50 = 10.4, p<0.0002; **: p<0.01, ***: p<0.001, Bonferonni post-test vs. CORT/veh). N = 13-25 mice per group. (C) Acute treatment with either VU6001966 or VU0650786 increased the latency to immobility in the FST in CORT-conditioned mice (F2,59 = 6.0, p<0.0001; ***: p<0.001, ****: p<0.0001, Bonferonni post-test vs. CORT/veh). N = 16-27. (D) Acute treatment with either VU6001966 or VU0650786 increased the latency to immobility in the TST in CORT-treated mice (F2,52 = 7.8, p<0.002; *: p<0.05, **: p<0.001, Bonferonni post-test vs. CORT/veh). N = 11-25. (E) Mice underwent CVS for 4 weeks and behavioral studies were conducted 1-2 weeks after the cessation of CVS treatment. (F) Acute treatment with either VU6001966 or VU0650786 reversed CVS-induced anhedonia (F2,25 = 8.9, p<0.002; **: p<0.001, Bonferonni post-test vs. CVS/veh). N = 6-11. (G) Acute treatment with VU0650786 increased the latency to immobility in the FST in CVS-treated mice (F2,36 = 18.1, p<0.0001; ****: p<0.0001, Bonferonni post-test vs. CVS/veh). N = 13. (H) Acute treatment with either VU6001966 or VU0650786 increased the latency to immobility in the TST in CVS mice (F2,42 = 8.8, p<0.001; **: p<0.01, Bonferonni post-test vs. CVS/veh). N = 13.