Isolation-induced decreases in PDE11A4 expression are sufficient to impair subsequent social behavior. (A) Socially isolated (SI) C57BL/6J mice expressed significantly less PDE11A4 protein in the membrane compartment of the ventral hippocampal formation (VHIPP) relative to group-housed (GH) C57BL/6J mice (F(1,12) = 5.65, P = 0.035; n = 7 biological replicates (five males + two females)/group). (B) Isolation, then, induced a dose–response shift across PDE11A genotypes such that isolated PDE11A wild-type (WT) mice exhibited a behavioral profile similar to that of GH PDE11A heterozygous (HT) mice in social approach (assessed in males only, F(10,156) = 2.61, P = 0.006). WT-GH, n = 16; WT-SI, n = 12; HT-GH, n = 14; HT-SI, n = 15; KO-GH, n = 16; KO-SI, n = 11. (C) Similarly, isolated HTs shifted their behavioral profile towards that of PDE11A knockout (KO) mice in 24-h long-term memory for social odor recognition (F(2,58) = 5.43, P = 0.007). All males except where noted: WT-GH, n = 17; WT-SI, n = 9; HT-GH, n = 17 (includes three females); HT-SI, n = 14 (includes four females); KO-GH, n = 10; KO-SI, n = 5. #WT-GH, P < 0.03–0.001; *vs. novel object/familiar odor, P ⩽ 0.002; @vs. GH, P = 0.019–0.003.