Anxiety is presumably driven by fear memory. The nucleus accumbens involves emotional regulation. Molecular profiles in the nucleus accumbens related to stress-induced fear memory remain elucidated. Fear memory in mice was induced by a paradigm of social defeat. Physical and psychological stress was delivered to an intruder that was attacked by an aggressive resident. Meanwhile, an observer experienced psychological stress by seeing aggressor attacks. The nucleus accumbens tissues from intruder and observer mice that appear fear memory and anxiety as well as control mice were harvested for analyses of mRNA and miRNA profiles by high throughput sequencing. In the nucleus accumbens of intruders and observers with fear memory and anxiety, genes encoding AdrRα, AChRM2/3, GluRM2/8, HrR1, SSR, BDNF and AC are upregulated, while genes encoding DR3/5, PR2, GPγ8 and P450 are downregulated. Physical and/or psychological stress leads to fear memory and anxiety likely by molecules relevant to certain synapses. Moreover, there are differential expressions in genes that encode GABAR, 5-HTR1/5, CREB3, AChRM2, RyR, Wnt and GPγ13 in the nucleus accumbens from intruders versus observers. GABAergic, serotonergic and cholinergic synapses as well as calcium, Wnt and CREB signaling molecules may be involved in fear memory differently induced by psychological stress and physical/psychological stress. The data from analyzing mRNA and miRNA profiles are consistent. Some molecules are validated by qRT-PCR and dual luciferase reporter assay. Fear memory and anxiety induced by the mixture of physical and psychological stress or psychological stress appear influenced by complicated molecular mechanisms in the nucleus accumbens.