Effects of mGluR1 and mGluR5 antagonists on social interaction and mTORC1 signaling in wild-type mice. A, JNJ16259285 and fenobam impaired social preference at the higher doses (1 mg/kg for JNJ16259285 and 10 mg/kg for fenobam), but not at lower doses (0.3 mg/kg for JNJ16259285 and 3 mg/kg for fenobam; vehicle-treated mice, n = 20; for all other groups, n = 7. C, Center). B, At doses that did not affect the social preference, JNJ16259285 and fenobam were effective in reducing S6 ribosomal protein phosphorylation in the hippocampus of wild-type mice but not in Eif4ebp2-null mice. Twenty-four hours after injection, the short-term effect of JNJ16259285 and fenobam disappeared in wild-type mice, but fenobam had a delayed effect in reducing pS6 in 4E-BP2 knock-out mice; representative Western blots are presented in the top (asterisk indicates a residual signal of the anti-tS6 antibody when probing for GAPDH). Eif4ebp2+/+ plus vehicle, n = 10; Eif4ebp2+/+ plus JNJ16259285 at 0.5 h, n = 12; Eif4ebp2+/+ plus fenobam at 0.5 h, n = 11; Eif4ebp2+/+ plus JNJ16259285 at 24 h, n = 3; Eif4ebp2+/+ plus fenobam at 24 h, n = 3; Eif4ebp2−/− plus vehicle, n = 10; Eif4ebp2−/− plus JNJ16259285 at 0.5 h, n = 5; Eif4ebp2−/− plus fenobam at 0.5 h, n = 5; Eif4ebp2−/− plus JNJ16259285 at 24 h, n = 5; and Eif4ebp2−/− plus fenobam at 24 h, n = 8 mice per group. N.S., Not significant. *p < 0.05, **p < 0.01, and ***p < 0.001.